Sample records for abscessus lung disease

Full Text Available BACKGROUND: Little is known about the nature of the host immune response to Mycobacterium abscessus complex (MABC infection. The aim of the present study was to investigate whether alterations in serum immunomolecule levels after treating MABC lungdisease patients with antibiotics can reflect the disease-associated characteristics. METHODS: A total of 22 immunomolecules in 24 MABC lungdisease patients before and after antibiotic therapy were quantitatively analyzed using a multiplex bead-based system. RESULTS: In general, the pre-treatment levels of T helper type 1 (Th1-related cytokines, i.e., interferon (IFN-γ and interleukin (IL-12, and Th2-related cytokines, i.e., IL-4 and IL-13, were significantly decreased in patients compared with control subjects. In contrast, the pre-treatment levels of Th17-related cytokines, i.e., IL-17 and IL-23, were significantly increased in MABC patients. Interestingly, significantly higher levels of IFN-γ-induced protein (IP-10 and monokine induced by IFN-γ protein (MIG were detected in patients with failure of sputum conversion at post-treatment compared to patients with successful sputum conversion. CONCLUSION: Reduced Th1 and Th2 responses and enhanced Th17 responses in patients may perpetuate MABC lungdisease, and the immunomolecules IP-10 and MIG, induced through IFN-γ, may serve as key markers for indicating the treatment outcome.

Current regimens used to treat pulmonary Mycobacterium abscessusdisease have limited efficacy. There is an urgent need for new drugs and optimized combinations and doses. We performed hollow-fiber-system studies in which M. abscessus was exposed to moxifloxacin lung concentration-time profiles similar to human doses of between 0 and 800 mg/day. The minimum bactericidal concentration and MIC were 8 and 2 mg/liter, respectively, in our M. abscessus strain, suggesting bactericidal activity. Measurement of the moxifloxacin concentrations in each hollow-fiber system revealed an elimination rate constant (kel) of 0.11 ± 0.05 h(-1) (mean ± standard deviation) (half-life of 9.8 h). Inhibitory sigmoid maximal effect (Emax) modeling revealed that the highest Emax was 3.15 ± 1.84 log10 CFU/ml on day 3, and the exposure mediating 50% of Emax (EC50) was a 0- to 24-h area under the concentration time curve (AUC0-24)-to-MIC ratio of 41.99 ± 31.78 (r(2) = 0.99). The EC80 was an AUC0-24/MIC ratio of 102.11. However, no moxifloxacin concentration killed the bacteria to burdens below the starting inoculum. There was regrowth beyond day 3 in all doses, with replacement by a resistant subpopulation that had an MIC of >32 mg/liter by the end of the experiment. A quadratic function best described the relationship between the AUC0-24/MIC ratio and the moxifloxacin-resistant subpopulation. Monte Carlo simulations of 10,000 patients revealed that the 400- to 800-mg/day doses would achieve or exceed the EC80 in ≤12.5% of patients. The moxifloxacin susceptibility breakpoint was 0.25 mg/liter, which means that almost all M. abscessus clinical strains are moxifloxacin resistant by these criteria. While moxifloxacin's efficacy against M. abscessus was poor, formal combination therapy studies with moxifloxacin are still recommended. PMID:27067317

When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lungdisease have difficulty breathing. Millions of people in ...

Diffuse parenchymal lungdisease; Alveolitis; Idiopathic pulmonary pneumonitis (IPP) ... The lungs contain tiny air sacs (alveoli), which is where oxygen is absorbed. These air sacs expand with each ...

Inhalational lungdiseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lungdiseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become ...

... called pulmonary fibrosis. Breathing in dust or other particles in the air is responsible for some types of interstitial lungdiseases. Specific types include Black lungdisease among coal miners, from inhaling coal dust Farmer's lung, from inhaling farm dust Asbestosis, from inhaling ...

To the Editor: Nontuberculous mycobacteria (NTM) are increasingly recognized as human pathogens (1). Otomastoiditis is a rare extrapulmonary NTM disease type first described in 1976; Mycobacterium chelonae-M. abscessus group bacteria, which are rapidly growing NTM, are the most frequent causative ag

Keith Simmon, scientist at Isentio US discusses research that was done while he was at ARUP laboratories, discusses a new classification of Mycobacterium chelonae-abscessus complex. Created: 11/17/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). Date Released: 11/22/2011.

... Share this page from the NHLBI on Twitter. LungDiseases and Conditions Breathing is a complex process. If ... lead to a disease called COPD (chronic obstructive pulmonary disease). COPD prevents proper airflow in and out of ...

Over the last 10 years, Mycobacterium abscessus group strains have emerged as important human pathogens, which are associated with significantly higher fatality rates than any other rapidly growing mycobacteria. These opportunistic pathogens are widespread in the environment and can cause a wide range of clinical diseases, including skin, soft tissue, central nervous system, and disseminated infections; by far, the most difficult to treat is the pulmonary form. Infections with M. abscessus ar...

Full Text Available Interstitial lungdiseases are a group of diffuse parenchymal lung disorders associated with substantial morbidity and mortality. Knowledge achieved in recent years has resulted in the publication of the new classification of idiopathic interstitial pneumonias, according to which there are three groups: major, rare and unclassified. The novelty of the new classification comes from the fact that difficult to classify entities can be treated according to the disease behaviour classification. Idiopathic pulmonary fibrosis is the most lethal amongst the interstitial lungdiseases and presents high heterogeneity in clinical behaviour. A number of biomarkers have been proposed in order to predict the course of the disease and group patients with the same characteristics in clinical trials. Early diagnosis and disease stratification is also important in the field of other interstitial lungdiseases.

Full Text Available Multiple cystic lungdisease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt–Hogg–Dubé; other rare causes of cystic lungdisease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lungdisease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lungdisease, and guides diagnostic evaluation and management.

Multiple cystic lungdisease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lungdisease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lungdisease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lungdisease, and guides diagnostic evaluation and management. PMID:26621970

... depending on the cause. Importantly, each person responds differently to treatment, so close monitoring during treatment is important. More Interstitial LungDisease ... a Question Learn About Clinical Trials Find a Doctor Find Departments ...

Multiple cystic lungdisease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and a...

A 70-year-old female with seronegative rheumatoid arthritis developed interstitial pneumonitis while on chrysotherapy. The reversibility of lungdisease and favourable response to steroid treatment support the diagnosis of gold-induced lungdisease and distinguish this entity from other forms of interstitial lungdisease associated with rheumatoid arthritis. The relevant literature related to gold-induced lungdisease is briefly reviewed.

Full Text Available Mycobacterium abscessus is an emerging rapidly growing mycobacterium (RGM causing a pseudotuberculous lungdisease to which patients with cystic fibrosis (CF are particularly susceptible. We report here its complete genome sequence. The genome of M. abscessus (CIP 104536T consists of a 5,067,172-bp circular chromosome including 4920 predicted coding sequences (CDS, an 81-kb full-length prophage and 5 IS elements, and a 23-kb mercury resistance plasmid almost identical to pMM23 from Mycobacterium marinum. The chromosome encodes many virulence proteins and virulence protein families absent or present in only small numbers in the model RGM species Mycobacterium smegmatis. Many of these proteins are encoded by genes belonging to a "mycobacterial" gene pool (e.g. PE and PPE proteins, MCE and YrbE proteins, lipoprotein LpqH precursors. However, many others (e.g. phospholipase C, MgtC, MsrA, ABC Fe(3+ transporter appear to have been horizontally acquired from distantly related environmental bacteria with a high G+C content, mostly actinobacteria (e.g. Rhodococcus sp., Streptomyces sp. and pseudomonads. We also identified several metabolic regions acquired from actinobacteria and pseudomonads (relating to phenazine biosynthesis, homogentisate catabolism, phenylacetic acid degradation, DNA degradation not present in the M. smegmatis genome. Many of the "non mycobacterial" factors detected in M. abscessus are also present in two of the pathogens most frequently isolated from CF patients, Pseudomonas aeruginosa and Burkholderia cepacia. This study elucidates the genetic basis of the unique pathogenicity of M. abscessus among RGM, and raises the question of similar mechanisms of pathogenicity shared by unrelated organisms in CF patients.

Full Text Available Inhalational lungdiseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lungdiseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become apparent several years after exposure to the particles. However, for certain types of dusts, e.g., silicone dioxide crystal and beryllium, heavy exposure within a short period can cause an acute disease. Pulmonary involvement in asbestosis is usually in the lower lobes. On the contrary, in silicosis and coal worker pneumoconiosis, the upper lobes are involved predominantly. For imaging evaluation of pneumoconiosis, high-resolution computed tomography (CT is superior to conventional chest x-ray. Magnetic resonance imaging (MRI and positron emission tomography (PET scan are helpful in those with suspected tumoral lesions. In this essay, we reviewed the imaging aspects of inhalational lungdisease.

Mycobacterium abscessus complex (M. abscessus subsp. abscessus and M. abscessus subsp. bolletii) is an emerging pathogen causing various human infections. However, few studies have focused on M. abscessus complex bacteraemia with detailed species differentiation. The clinical characteristics of patients with bacteraemia due to M. abscessus complex treated at National Taiwan University Hospital from 2005-2012 were evaluated. Species identification was performed by molecular methods, and minimum inhibitory concentrations (MICs) were determined using a Sensititre RAPMYCO Panel Test for preserved M. abscessus complex isolates. During the study period, 15 patients with M. abscessus complex bacteraemia were found but only 14 isolates from 13 patients were preserved for analysis. One patient had two episodes of bacteraemia (one caused by M. abscessus subsp. bolletii and one by M .abscessus subsp. abscessus with a 9-month interval). Of the remaining 12 patients, 9 patients had M. abscessus subsp. bolletii bacteraemia and 3 had M .abscessus subsp. abscessus bacteraemia. Patients were mainly middle-aged adults with various co-morbidities. Steroid usage and malignancy (5/15) were the most common immunocompromised statuses, followed by diabetes mellitus (4/15). Surgical wound infection was the most common infection foci in all patients (5/15), particularly in M. abscessus subsp. bolletii bacteraemia patients. Clarithromycin and tigecycline exhibited good in vitro activities. Overall, the 14-day mortality was 20% (3/15). M. abscessus complex bacteraemia should be considered an emerging opportunistic infection in immunocompromised hosts. Clarithromycin and tigecycline have potent in vitro activities and are promising agents for treating infections due to M. abscessus complex. PMID:24718088

For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lungdiseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lungdiseases (ILDs). Indeed, there are three diseases, namely respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currentl...

Over the last 10 years, Mycobacterium abscessus group strains have emerged as important human pathogens, which are associated with significantly higher fatality rates than any other rapidly growing mycobacteria. These opportunistic pathogens are widespread in the environment and can cause a wide range of clinical diseases, including skin, soft tissue, central nervous system, and disseminated infections; by far, the most difficult to treat is the pulmonary form. Infections with M. abscessus are often multidrug-resistant (MDR) and require prolonged treatment with various regimens and, many times, result in high mortality despite maximal therapy. We report here the evaluation of diverse mouse infection models for their ability to produce a progressive high level of infection with M. abscessus. The nude (nu/nu), SCID (severe combined immunodeficiency), gamma interferon knockout (GKO), and granulocyte-macrophage colony-stimulating factor (GMCSF) knockout mice fulfilled the criteria for an optimal model for compound screening. Thus, we set out to assess the antimycobacterial activity of clarithromycin, clofazimine, bedaquiline, and clofazimine-bedaquiline combinations against M. abscessus-infected GKO and SCID murine infection models. Treatment of GKO and SCID mice with a combination of clofazimine and bedaquiline was the most effective in decreasing the M. abscessus organ burden. PMID:26303795

The authors discuss their approach to the diagnosis and management of patients with DILD. Gallium scans play a central role in this process. Not only do they help them decide whom to biopsy, but also where to biopsy. The scans can be used for the early detection of disease in a high-risk population, for following the progression and regression of disease, for the regulation of medication, and for the evaluation of therapy. Bronchoalveolar lung lavage appears to be equally sensitive. However, patients are less willing to undergo repeated fiberoptic bronchoscopies than lung scans. Both tests may prove useful, one complementing the other. Gallium imaging has also been utilized by the authors in select patients with questionable diffuse lung infiltrates roentgenographically or with a normal chest roentgenogram, chronic respiratory symptoms, and abnormal pulmonary function studies. An abnormal gallium lung scan in these clinical situations helps them select which patients have a diffuse active pulmonary process meriting transbronchial biopsies. This has proven to be of particular value in the management of older patients

Full Text Available Congenital cystic diseases of the lung are a rare but significant cause of morbidity in children and young adults presenting with respiratory distress and repeated chest infections. They consist of cystic adenomatoid malformation, bronchogenic cyst, pulmonary sequestration, and congenital lobar emphysema. Surgical treatment is a safe and an effective method of treatment. Chest X-ray and computed tomography are the key imaging modalities used for diagnosis.

The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell ...

Early signs of pulmonary disease with Mycobacterium abscessus complex (MABSC) can be missed in patients with cystic fibrosis (CF). A serological method could help stratify patients according to risk. The objective of this study was to test the diagnostic accuracy of a novel method for investigating...

... page from the NHLBI on Twitter. What Are Asbestos-Related LungDiseases? Asbestos-related lungdiseases are ... as the peritoneum (PER-ih-to-NE-um). Asbestos-Related LungDiseases Figure A shows the location ...

Occupational and environmental lungdisease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lungdisease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lungdisease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures. PMID:26024603

Full Text Available Aspergillus is a ubiquitous dimorphic fungus that causes a variety of human diseases ranging in severity from trivial to life-threatening, depending on the host response. An intact host defence is important to prevent disease, but individuals with pre-existing structural lungdisease, atopy, occupational exposure or impaired immunity are susceptible. Three distinctive patterns of aspergillus-related lungdisease are recognized: saprophytic infestation of airways, cavities and necrotic tissue; allergic disease including extrinsic allergic alveolitis, asthma, allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis and chronic eosinophilic pneumonia; and airway and tissue invasive disease -- pseudomembranous tracheobronchitis, acute bronchopneumonia, angioinvasive aspergillosis, chronic necrotizing aspergillosis and invasive pleural disease. A broad knowledge of these clinical presentations and a high index of suspicion are required to ensure timely diagnosis and treatment of the potentially lethal manifestations of aspergillus-related pulmonary disease. In the present report, the clinical, radiographic and pathological aspects of the various aspergillus-related lungdiseases are briefly reviewed.

Full Text Available Introduction. Interstitial lungdiseases include a heterogeneous group of disorders that may affect men and women, but some of them are more frequent in females. Therefore, it is very important to take into account the female gender as a specific risk factor for some of these diseases. Discussion and Review of Literature. Interstitial lungdiseases in women include the following: 1. diseases specific for female gender such as lymphangioleiomyomatosis, 2. disorders predominant in women due to the underlying disease (breast cancer and collagen vascular diseases: systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, dermatomyositis and polymyositis, Sjögren syndrome, 3. idiopathic lungdiseases predominant in women such an idiopathic eosinophilic pneumonia, 4. interstitial lungdiseases predominant in women for unknown reason. All of these diseases have a wide spectrum of thoracic manifestations. Chest x-ray is a basic method for the detection, but computerized tomography is more useful for the assessment of the extensivity of parenchymal, airway and pleural manifestations of these diseases. Conclusion. A great variety of manifestations of interstitial lungdiseases in women makes their detailed review impossible. Therefore, this article gives a short and overall review of these conditions. [Projekat Ministarstva nauke Republike Srbije, br. 175046 i br. 175081

Full Text Available Mycobacterium abscessus infections rarely develop in healthy individuals, and mostly they occur in immunocompromised hosts. Vertebral osteomyelitis due to Mycobacterium abscessus is very rare and only three previous cases of spinal infection caused by Mycobacterium abscessus have been reported. Mycobacterium abscessus isolates are uniformly resistant to antituberculous agents and can display a virulent biofilm-forming phenotype. The patient was a 67-year-old woman with vertebral osteomyelitis of the L1-2. She was healthy without immune-suppressed condition, history of trauma, or intravenous drug use. The smear examination of the specimen harvested by CT-guided puncture of the paravertebral abscess revealed Mycobacterium abscessus. Her disease condition did not abate with conservative treatment using antimicrobial chemotherapy. Radical debridement of the vertebral osteomyelitis and anterior reconstruction from T12 to L2 using antibacterial iodine-supported instrumentation were performed. Chemotherapy using clarithromycin, amikacin, and imipenem was applied for 6 months after surgery as these antibiotics had been proven to be effective to Mycobacterium abscessus after surgery. Two years after surgery, the infected anterior site healed and bony fusion was successfully achieved without a recurrence of infection.

Full Text Available For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lungdiseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lungdiseases (ILDs. Indeed, there are three diseases, namely respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currently considered aetiologically linked to smoking and a few others which are more likely to develop in smokers. Here, we aim to focus on the most recent findings regarding the role of smoking in the pathogenesis and clinical behaviour of ILDs.

For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lungdiseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lungdiseases (ILDs). Indeed, there are three diseases, namely respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currently considered aetiologically linked to smoking and a few others which are more likely to develop in smokers. Here, we aim to focus on the most recent findings regarding the role of smoking in the pathogenesis and clinical behaviour of ILDs. PMID:26324804

In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to four-fold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in...

... will receive oxygen therapy in their home . A respiratory therapist will help you set up the oxygen. Families need to learn proper oxygen storage and safety . Lung rehabilitation can provide support, and help you learn: Different ...

Work-related respiratory diseases affect people in every industrial sector, constituting approximately 60% of all disease and injury mortality and 70% of all occupational disease mortality. There are two basic types: interstitial lungdiseases, that is the pneumoconioses (asbestosis, byssinosis, chronic beryllium disease, coal workers' pneumoconiosis (CWP), silicosis, flock workers' lung, and farmers' lungdisease), and airways diseases, such as work-related or exacerbated asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans (a disease that was recognized in the production of certain foods only 10 years ago). Common factors in the development of these diseases are exposures to dusts, metals, allergens and other toxins, which frequently cause oxidative damage. In response, the body reacts by activating primary immune response genes (i.e. cytokines that often lead to further oxidative damage), growth factors and tissue remodelling proteins. Frequently, complex imbalances in these processes contribute to the development of disease. For example, tissue matrix metalloproteases can cause the degradation of tissue, as in the development of CWP small profusions, but usually overexpression of matrix metalloproteases is controlled by serum protein inhibitors. Thus, disruption of such a balance can lead to adverse tissue damage. Susceptibility to these types of lungdisease has been investigated largely through candidate gene studies, which have been characteristically small, often providing findings that have been difficult to corroborate. An important exception to this has been the finding that the HLA-DPB11(E69) allele is closely associated with chronic beryllium disease and beryllium sensitivity. Although chronic beryllium disease is only caused by exposure to beryllium, inheritance of HLA-DPB1(E69) carries an increased risk of between two- and 30-fold in beryllium exposed workers. Most, if not all, of these occupationally related diseases are

Aspiration is a common but underrecognized clinicopathologic entity, with varied radiographic manifestations. Aspiration represents a spectrum of diseases, including diffuse aspiration bronchiolitis, aspiration pneumonitis, airway obstruction by foreign body, exogenous lipoid pneumonia, interstitial fibrosis, and aspiration pneumonia with or without lung abscess formation. Many patients who aspirate do not present with disease, suggesting that pathophysiology is related to a variety of factors, including decreased levels of consciousness, dysphagia, impaired mucociliary clearance, composition of aspirate, and impaired host defenses. In this pictorial essay, we will review the different types of aspiration lungdiseases, focusing on their imaging features and differential diagnosis. PMID:24911122

The interstitial lungdiseases (ILD)s are a diverse group of pulmonary disorders that are classified together because of similar clinical, roentgenographic, physiologic, or pathologic manifestations, compromising over 100 different members that have been broadly classified into several categories. The major abnormality in ILDs is disruption of the lung parenchyma. Sarcoidosis is the commonest ILD in the western world. In our own experience, hypersensitivity pneumonitis is also quite common in...

Abstract Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lungdisease, pneumo...

The interstitial lungdiseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lungdiseases and introduced the term diffuse parenchymal lungdisease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lungdisease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lungdisease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lungdiseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lungdiseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lungdisease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lungdiseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lungdiseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lungdiseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lungdiseases during the past decade, research in these diseases is urgently needed. PMID:19170214

Full Text Available Interstitial lungdisease (ILD is a final common pathway of a broad heterogeneous group of parenchymal lung disorders. It is characterized by progressive fibrosis of the lung leading to restriction and diminished oxygen transfer. Clinically, the presenting symptoms of ILD are non-specific (cough and progressive dyspnea on exertion and are often attributed to other diseases, thus delaying diagnosis and timely therapy. Clues from the medical history along with the clinical context and radiologic findings provide the initial basis for prioritizing diagnostic possibilities for a patient with ILD. An accurate prognosis and optimal treatment strategy for patients with ILDs can only be after an accurate diagnosis. This review will assist pulmonary physicians and medicine specialist in recognition of ILD. Extensive literature search has been made through PubMed and also Book References has been used for writing this review.

Full Text Available Abstract Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lungdisease, pneumonia, and alveolar proteinosis. Understanding of the mechanisms that disturb the lung surfactant system may lead to novel rational therapies for these diseases.

The results presented in this review suggest that the impact of nutrition on obstructive lungdisease is most evident for antioxidant vitamins, particularly vitamin C and, to a lesser extent, vitamin E. By decreasing oxidant insults to the lung, antioxidants could modulate the development of chronic lungdiseases and lung function decrement. Antioxidant vitamins could also play an important role in gene-environment interactions in complex lungdiseases such as childhood asthma. Data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements; however, relevant data are still sparse. Although epidemiologic data suggest that consumption of fresh fruit may reduce risk of noncarcinogenic airway limitation, there are no clear data on which nutrients might be most relevant. While some studies evaluate daily intake of vitamin C, other studies use fruit consumption as a surrogate for antioxidant intake. Given the dietary intercorrelations among antioxidant vitamins, particularly vitamin C, beta-carotene, and flavonoids, as well as other micronutrients, it may be difficult to isolate a specific effect. Some population subgroups with higher levels of oxidative stress, such as cigarette smokers, may be more likely to benefit from dietary supplementation, since some studies have suggested that antioxidant intake may have a greater impact in this group. Studies of lung function decrement and COPD in adults suggest that daily intake of vitamin C at levels slightly exceeding the current Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among smokers) may have a protective effect (20). In the Schwartz and Weiss (85) and Britton et al. (87) studies, an increase of 40 mg/day in vitamin C intake led to an approximate 20-ml increase in FEV1. Daily mean vitamin C intakes in these studies were 66 mg and 99.2 mg, respectively, and the highest intake level (178 mg/day) was approximately

This paper begins with a discussion of the 1980 International Labour Organization classification of the pneumoconioses. Emphasis is on the common pneumoconioses, that is, silicosis, coalworker's pneumoconiosis, and asbestos-related pleural and parenchymal disease. Examples of the five radiographic forms of silicosis-simple and complicated silicosis, Caplan syndrome, silicotuberculosis, and acute silicosis- are presented, and the differential diagnoses are discussed. Discussion of asbestos-related disease included pleural manifestations such as plaques, diffuse pleural thickening, and asbestos pleural effusion as well as asbestosis and malignancies associated with asbestos exposure, such as bronchogenic carcinoma and malignant mesothelioma. Although the standard radiographic findings are stressed, the use of CT in the diagnosis of pneumoconiosis and the staging of dust-related malignancies is also discussed

Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lungdiseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte-to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lungdisease and confirm the importance of pericytes in human fibrotic pulmonary disease. PMID:25034005

Abstract Interstitial lungdisease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathologic...

High resolution CT (computerized tomography) was discussed in detail. The conclusions were HRCT is able to define lung anatomy at the secondary lobular level and define a variety of abnormalities in patients with diffuse lungdiseases. Evidence from numerous studies indicates that HRCT can play a major role in the assessment of diffuse infiltrative lungdisease and is indicate clinically (95 refs.)

Objectives Interstitial lungdiseases (ILD) are heterogenous groups of disorders that involve the interstitium of the lung. Lung biopsy is mandatory in most cases of ILD for diagnosis. In Korea, a few clinical data about ILD were analyzed on the basis of pathologic proof. Thus, we analysed the clinical profiles of patients with ILD who had lung biopsy in a tertiary university hospital. Methods Clinical and pathologic data concerning 100 patients who had open lung biopsy (OLB) and/or transbron...

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lungdiseases such as interstitial lungdiseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lungdiseases, some of which are very common, the available data is limited. In this ...

Full Text Available Abstract Interstitial lungdisease (ILD in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1 exposure-related ILD; 2 systemic disease-associated ILD; 3 alveolar structure disorder-associated ILD; and 4 ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.

Although it has been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as a means of distinguishing pulmonary embolism (P.E.) from COPD is reported. Recent experience is reported with the use of both of these procedures in comparison with pulmonary function tests for the early detection of COPD in population studies and also in P.E. suspects. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imaging in the differential diagnosis of P.E. Finally, this paper is concerned with new developments in regional lung diffusion imaging following the inhalation of radioactive gases and rapidly absorbed radioaerosols. Their experimental basis is presented and their potential clinical applications in pulmonary embolism are discussed. As a result of these investigations, a functional (V/P) diagnosis of pulmonary embolism in patients may be possible in the near future with a sequential radioaerosol inhalation procedure alone

Right ventricular dysfunction arises in chronic lungdisease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lungdisease, and more frequently complicates advanced lungdisease. Right ventricular failure is rare, ex...

... fully expand the lungs). Lung volumes may show hyperinflation (i.e., too much air in the lungs ... X-rays are usually normal but may show hyperinflation. High-resolution computerized tomography (HRCT) scans of the ...

Full Text Available Interstitial lungdiseases (ILDs represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lungdiseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis.

The diffuse cystic lungdiseases (DCLDs) are a group of pathophysiologically heterogenous processes that are characterized by the presence of multiple spherical or irregularly shaped, thin-walled, air-filled spaces within the pulmonary parenchyma. Although the mechanisms of cyst formation remain incompletely defined for all DCLDs, in most cases lung remodeling associated with inflammatory or infiltrative processes results in displacement, destruction, or replacement of alveolar septa, distal airways, and small vessels within the secondary lobules of the lung. The DCLDs can be broadly classified according to underlying etiology as those caused by low-grade or high-grade metastasizing neoplasms, polyclonal or monoclonal lymphoproliferative disorders, infections, interstitial lungdiseases, smoking, and congenital or developmental defects. In the first of a two-part series, we present an overview of the cystic lungdiseases caused by neoplasms, infections, smoking-related diseases, and interstitial lungdiseases, with a focus on lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis. PMID:25906089

Full Text Available Clarithromycin was considered the cornerstone for the treatment of Mycobacterium abscessus complex infections. Genetic resistance mechanisms have been described and many experts propose amikacin as an alternative. Nevertheless, clarithromycin has several advantages; therefore, it is necessary to identify the non-functional erm(41 allele to determine the most suitable treatment. The aims of this study were to characterize the molecular mechanisms of clarithromycin resistance in a collection of Mycobacterium abscessus complex isolates and to verify the relationship between these mechanisms and the antibiogram.Clinical isolates of M. abscessus complex (n = 22 from 16 patients were identified using four housekeeping genes (rpoB, secA1, sodA and hsp65, and their genetic resistance was characterized by studying erm(41 and rrl genes. Nine strains were recovered from the clinical isolates and subjected to E-test and microdilution clarithromycin susceptibility tests, with readings at 3, 7 and 14 days.We classified 11/16 (68.8% M. abscessus subsp. abscessus, 4/16 (25.0% M. abscessus subsp. bolletii, and 1/16 (6.3% M. abscessus subsp. massiliense. T28 erm(41 allele was observed in 8 Mycobacterium abscessus subps. abscessus and 3 Mycobacterium abscessus subsp. bolletii. One strain of M. abscessus subsp. bolletii had an erm(41 gene truncated and was susceptible to clarithromycin. No mutations were observed in rrl gene first isolates. In three patients, follow-up of initial rrl wild-type strains showed acquired resistance.Most clinical isolates of M. abscessus complex had inducible resistance to clarithromycin and total absence of constitutive resistance. Our findings showed that the acquisition of resistance mutations in rrl gene was associated with functional and non-functional erm(41 gene. Caution is needed when using erm(41 sequencing alone to identify M. abscessus subspecies. This study reports an acquired mutation at position 2057 of rrl gene

The intrinsic and acquired resistance of Mycobacterium abscessus to commonly used antibiotics limits the chemotherapeutic options for infections caused by these mycobacteria. Intrinsic resistance is attributed to a combination of the permeability barrier of the complex multilayer cell envelope, drug export systems, antibiotic targets with low affinity and enzymes that neutralize antibiotics in the cytoplasm. To date, acquired resistance has only been observed for aminoglycosides and macrolides, which is conferred by mutations affecting the genes encoding the antibiotic targets (rrs and rrl, respectively). Here we summarize previous and recent findings on the resistance of M. abscessus to antibiotics in light of what has been discovered for other mycobacteria. Since we can now distinguish three groups of strains belonging to M. abscessus (M. abscessus sensu stricto, Mycobacterium massiliense and Mycobacterium bolletii), studies on antibiotic susceptibility and resistance should be considered according to this new classification. This review raises the profile of this important pathogen and highlights the work needed to decipher the molecular events responsible for its extensive chemotherapeutic resistance. PMID:22290346

Interstitial lungdisease is one of the most serious side effects caused by lung cancer treatment. Due to the complexity diagnosis and variability of the disease, it is often not diagnosied and treated in time, even endanger the patient's life and affect the patient's prognosis. The mechanism of interstitial pneumonia caused by radiotherapy, chemotherapy and targeted therapy is still not fully known. Therefore, it become a problem that how to early detection, diagnosis and treat the interstit...

There is increasing recognition that the sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lungdiseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are...

Four cases of the triad of rheumatoid lungdisease, spontaneous pneumothorax, and peripheral blood eosinophilia are reported. Cavitation of a rheumatoid lung nodule caused the pneumothorax in at least 1 case. The significance of eosinophilia and its value as a marker of extra-articular manifestations of rheumatoid disease are discussed.

There are many different interstitial lungdiseases associated with smoking. This short review describes officially recognized disorders (desquamative interstitial pneumonia, respiratory bronchiolitis and pulmonary Langerhans´cells histiocytosis) and entities with uncertain relationship to smoking, which have recently been published in the literature. Histopathological pictures and differential diagnosis of smoking-related diseases of the lungs are discussed. PMID:27223588

Cigarette smoking has been implicated in the development of some uncommon respiratory interstitial diseases. Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lungdiseases are characterized by a diffuse alveolar and peribronchiolar filling with macrophages, respectively. Pulmonary Langerhans' cell histiocytosis is a rare interstitial lung disorder characterized by the proliferation of Langerhans' cell forming interstitial infiltrates and nodules that c...

Pulmonary hypertension (PH) is a common complication of interstitial lungdiseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lungdiseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. ...

The chest radiograph is the basic tool for identifying occupational and environmental lungdiseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lungdiseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lungdiseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory disease states. A number of ongoing randomized Phase I/II clinical trials are evaluating the effects of allogeneic MSC infusion in patients with multiple sclerosis, graft-versus-host disease, Crohn's disease, and severe chronic myocardial ischemia. MSCs are also being considered as a potential therapy in patients with inflammatory lungdiseases. Several studies, including our own, have demonstrated compelling benefits from the administration of MSCs in animal models of lung injury. These studies are leading to growing interest in the therapeutic use of MSCs in inflammatory lungdiseases. In this Review, we describe how the immunoregulatory effects of MSCs can confer substantial protection in the setting of lungdiseases such as acute lung injury, chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. We also address potential pitfalls related to the therapeutic use of MSCs in fibrotic lungdiseases such as idiopathic pulmonary fibrosis. In addition, we identify emerging areas for MSC- based therapies in modulating oxidative stress and in attenuating inflammation in alcohol-related acute lung injury. PMID:19352305

The diffuse cystic lungdiseases have a broad differential diagnosis. A wide variety of pathophysiological processes spanning the spectrum from airway obstruction to lung remodeling can lead to multifocal cyst development in the lung. Although lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are perhaps more frequently seen in the clinic, disorders such as Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, follicular bronchiolitis, and light-chain deposition disease are increasingly being recognized. Obtaining an accurate diagnosis can be challenging, and management approaches are highly disease dependent. Unique imaging features, genetic tests, serum studies, and clinical features provide invaluable clues that help clinicians distinguish among the various etiologies, but biopsy is often required for definitive diagnosis. In part II of this review, we present an overview of the diffuse cystic lungdiseases caused by lymphoproliferative disorders, genetic mutations, or aberrant lung development and provide an approach to aid in their diagnosis and management. PMID:25906201

Patients with diffuse interstitial lungdisease often require a lung biopsy to determine the diagnosis and proper therapy. However, once the diagnosis is established, clinical evaluation of symptoms, chest roentgenogram and pulmonary function testing are the only noninvasive means currently available to assess activity of the disease process and response to the therapy. Although these measures appear adequate in the presence of acute active disease in which response to therapy results in readily demonstrable changes in the above parameters, they may be insensitive to subtle changes that can occur in minimally active disease with slowly progressive interstitial pulmonary fibrosis over a period of years. A more sensitive noninvasive technique for identifying these cases with a smoldering diffuse interstitial inflammatory process might greatly improve our ability to effectively manage such patients. With this in mind, the value of gallium lung scan was investigated to assess its ability to predict inflammatory activity in such a clinical setting.

Patients with diffuse interstitial lungdisease often require a lung biopsy to determine the diagnosis and proper therapy. However, once the diagnosis is established, clinical evaluation of symptoms, chest roentgenogram and pulmonary function testing are the only noninvasive means currently available to assess activity of the disease process and response to the therapy. Although these measures appear adequate in the presence of acute active disease in which response to therapy results in readily demonstrable changes in the above parameters, they may be insensitive to subtle changes that can occur in minimally active disease with slowly progressive interstitial pulmonary fibrosis over a period of years. A more sensitive noninvasive technique for identifying these cases with a smoldering diffuse interstitial inflammatory process might greatly improve our ability to effectively manage such patients. With this in mind, the value of gallium lung scan was investigated to assess its ability to predict inflammatory activity in such a clinical setting

Background Interstitial lungdiseases (ILDs) are disorders of the lung parenchyma. The pathogenesis, clinical manifestations, and prognosis of ILDs vary depending on the underlying disease. The onset of most ILDs is insidious, but they may also present subacutely or require hospitalization for management. ILDs that may present subacutely include acute interstitial pneumonia, connective tissue disease-associated ILDs, cryptogenic organizing pneumonia, acute eosinophilic pneumonia, drug-induced...

BACKGROUND: Spirometry, the measurement of forced expiratory volume in 1 s and forced vital capacity, is recommended in the diagnosis and management of the obstructive lungdiseases asthma and chronic obstructive pulmonary disease (COPD). The present report describes spirometry use in Manitoba and tests the hypothesis that regional spirometry use correlates with the prevalence of physician-diagnosed obstructive lungdiseases.METHODS: Spirometry is remunerated on a fee-for-service basis by Man...

Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood-air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like

Full Text Available Urban air pollution is a serious worldwide problem due to its impact on human health. In the past sixty years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently Particulate matter (PM is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood-air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: Coarse particles (PM10 in upper airways and fine particles (PM2.5 can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of particulate matter has been associated with different toxicological outcomes on clinical, epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic and biological compounds. All these compounds are capable of modifying several biological activities including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS. These inflammatory mediators can activate different pathways such as MAP-kinases, NF-B, and stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive

The most important smoking-related interstitial lungdiseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lungdisease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis

Full Text Available The lung is a particularly vulnerable organ at the interface of the body and the exterior environment. It is constantly exposed to microbes and particles by inhalation. The innate immune system needs to react promptly and adequately to potential dangers posed by these microbes and particles, while at the same time avoiding extensive tissue damage. NOD-like receptors (NLRs represent a group of key sensors for microbes and damage in the lung. As such they are important players in various infectious as well as acute and chronic sterile inflammatory diseases, such as pneumonia, chronic obstructive lungdisease (COPD, acute lung injury/ARDS, pneumoconiosis and asthma. Activation of most known NLRs leads to the production and release of pro-inflammatory cytokines, and/or to the induction of cell death. We will review NLR functions in the lung during infection and sterile inflammation.

Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lungdiseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lungdisease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

Early detection and treatment of lungdisease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lungdisease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lungdisease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels. PMID:26846584

Full Text Available Joshua J Solomon, Kevin K BrownAutoimmune Lung Center and Interstitial LungDisease Program, National Jewish Health, Denver, CO, USAAbstract: Rheumatoid arthritis (RA is a systemic inflammatory disorder affecting 1% of the US population. Patients can have extra-articular manifestations of their disease and the lungs are commonly involved. RA can affect any compartment of the respiratory system and high resolution computed tomography (HRCT of the lung is abnormal in over half of these patients. Interstitial lungdisease is a dreaded complication of RA. It is more prevalent in smokers, males, and those with high antibody titers. The pathogenesis is unknown but data suggest an environmental insult in the setting of a genetic predisposition. Smoking may play a role in the pathogenesis of disease through citrullination of protein in the lung leading to the development of autoimmunity. Patients usually present in middle age with cough and dyspnea. Pulmonary function testing most commonly shows reduced diffusion capacity for carbon monoxide and HRCT reveals a combination of reticulation and ground glass abnormalities. The most common pattern on HRCT and histopathology is usual interstitial pneumonia (UIP, with nonspecific interstitial pneumonia seen less frequently. There are no large-scale well-controlled treatment trials. In severe or progressive cases, treatment usually consists of corticosteroids with or without a cytotoxic agent for 6 months or longer. RA interstitial lungdisease is progressive; over half of patients show radiographic progression within 2 years. Patients with a UIP pattern on biopsy have a survival similar to idiopathic pulmonary fibrosis.Keywords: rheumatoid arthritis, interstitial lungdisease, nonspecific interstitial pneumonia, usual interstitial pneumonia, anti-CCP

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lungdiseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lungdiseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

Restrictive lungdiseases are a heterogeneous group of conditions characterized by a restrictive pattern on spirometry and confirmed by a reduction in total lung volume. Patients with more severe symptoms may have a reduced diffusing capacity of the lung for carbon monoxide. Etiologies can be intrinsic with lung parenchymal involvement, as in interstitial lungdiseases, or extrinsic to the lung, as in obesity and neuromuscular disorders. Idiopathic pulmonary fibrosis is a chronic progressive interstitial pneumonia with fibrosis for which treatment is primarily supportive with oxygen therapy, pulmonary rehabilitation, and management of comorbid conditions. Newer drugs for idiopathic pulmonary fibrosis, such as pirfenidone and nintedanib, can slow disease progression. Referral for evaluation for lung transplantation is recommended for appropriate patients. Obstructive sleep apnea and obesity hypoventilation syndrome increasingly are common health issues, with symptoms that can include snoring, daytime somnolence, difficulty concentrating, fatigue, witnessed apneas, and morning headaches. Serum bicarbonate may serve as a biomarker in screening for subclinical obesity hypoventilation syndrome. Preoperative evaluations should assess pulmonary risk in addition to cardiac risk with a thorough history, laboratory tests, and functional capacity assessments. Optimization of management may include weight loss, pulmonary rehabilitation, oxygen therapy, and respiratory support. PMID:27576233

Interstitial lungdiseases (ILD, diffuse lungdiseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lungdiseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lungdiseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article. PMID:26234096

Environmental lungdiseases are caused by exposure to adverse environmental conditions, such as atmospheric pressure changes or the ingestion or inhalation of toxic agents. The development of environmental lungdiseases depends on the intensity and duration of exposure, the physiological and biological susceptibility of the host, and the toxic effects of the adverse environmental conditions encountered. A combination of clinical features, related exposure history, imaging findings, and a review of previous reports that support an association between exposure and the disease process is required for diagnosis

Pulmonary rehabilitation is a comprehensive multifaceted team approach for integrating medical management, coping skills, self-management techniques, and exercise reconditioning. It provides patients with chronic lungdisease the ability to adapt and live full and nearly normal lives. These changes are possible because the overall disability includes significant reversible components: Patients have bronchospasm, infection, and cor pulmonale; they respond to progressively impaired lungs by pro...

The present article is the second in a series on rare lungdiseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling...

Diffuse cystic lungdisease represents a diverse group of uncommon disorders with characteristic appearance on high resolution CT imaging. The combination of imaging appearance with clinical features and genetic testing where appropriate permits a confident and accurate diagnosis in the majority of the diseases without recourse for open lung biopsy. The mechanism of cyst development disease is unclear but in some disorders appears to be related to small airways obstruction. These diseases are incurable, with the exception of Langerhans cell histiocytosis which may spontaneously remit or resolve on smoking cessation. Disease progression is unpredictable; in general older patients have a more benign disease, while young patients may progress rapidly to respiratory failure. An understanding of the complications of cystic lungdisease and the appearance of disease progression is essential for the management of these patients. A number of these disorders are associated with malignancy, recognition of the potential tumors permits appropriate imaging surveillance. Due to the widespread use of CT, pulmonary cysts are increasingly discovered incidentally in an asymptomatic individual. The diagnostic challenge is to determine whether these cysts represent an early feature of a progressive disease or have no clinical significance. In the elderly population the cysts are unlikely to represent a progressive disease. In individuals <50 years further evaluation is recommended

Diffuse cystic lungdisease represents a diverse group of uncommon disorders with characteristic appearance on high resolution CT imaging. The combination of imaging appearance with clinical features and genetic testing where appropriate permits a confident and accurate diagnosis in the majority of the diseases without recourse for open lung biopsy. The mechanism of cyst development disease is unclear but in some disorders appears to be related to small airways obstruction. These diseases are incurable, with the exception of Langerhans cell histiocytosis which may spontaneously remit or resolve on smoking cessation. Disease progression is unpredictable; in general older patients have a more benign disease, while young patients may progress rapidly to respiratory failure. An understanding of the complications of cystic lungdisease and the appearance of disease progression is essential for the management of these patients. A number of these disorders are associated with malignancy, recognition of the potential tumors permits appropriate imaging surveillance. Due to the widespread use of CT, pulmonary cysts are increasingly discovered incidentally in an asymptomatic individual. The diagnostic challenge is to determine whether these cysts represent an early feature of a progressive disease or have no clinical significance. In the elderly population the cysts are unlikely to represent a progressive disease. In individuals <50 years further evaluation is recommended.

Interstitial lungdisease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (...

Background Mycobacterium abscessus (M.abscessus) can cause a variety of human infections,involving the lung,skin and soft tissues,and is generally believed to be acquired from environmental sources.The aim of this study was to investigate the molecular diversity and antibiotic susceptibility of M.abscessus isolates as the basis for strategies to improve control and management of infection.Methods Seventy M.abscessus isolates from patients attending the Guangzhou Thoracic Hospital were identified from 2003 to 2005 by biochemical tests,gas chromatography,polymerase chain reaction (PCR)-restriction analysis (PRA) of heat shock protein gene hsp65,and sequencing of the quinolone resistance determining regions (QRDRs) of gyrA.Susceptibilities to six antibiotics were determined by micro-broth dilution.Isolates were genotyped using randomly amplified polymorphic DNA (RAPD) analysis.Results Most isolates (63/70； 90％) were susceptible to amikacin but rates of susceptibility to other antibiotics varied from moderate,clarithromycin (60％) and imipenem (43％),to low for ciprofloxacin and ofloxacin (3％),and 87％ of isolates had intermediate susceptibility to cefoxitin.RAPD analysis showed that the 70 clinical isolates displayed 69 unique RAPD patterns.Conclusions The high genetic diversity of isolates suggests that they are not transmitted from person to person but,presumably,are acquired independently from environmental sources.M.abscessus isolates displayed variable levels of susceptibility to all antibiotics tested,other than amikacin,indicating a need for routine susceptibility testing to guide treatment.

Practicing pulmonologists are often faced with the question of whether a lungdisease is related to something in the patient's workplace, home, or recreational environment. Recognizing a lungdisease as exposure related creates both opportunities and obligations for clinicians. In addition to managing the patient, the obligation to consider risks to others and to prevent ongoing exposure is a challenge that requires diagnostic clarity and collaboration between multiple specialists. We present five illustrative case studies of patients with diffuse lungdiseases from environmental and occupational exposures in which communication between the pulmonologist, radiologist, and pathologist was essential for both medical and public health management. Diagnostic and treatment strategies as well as social and preventive interventions are reviewed, with key points for the practicing pulmonologist. PMID:19221960

OBJECTIVES: To determine the proportion of adult medical patients who have chronic obstructive pulmonary disease (COPD), using the Global initiative for Chronic Obstructive LungDisease guidelines (GOLD), and its relation to vascular disease. METHODS: This is a prospective cross-sectional study of adult patients admitted to acute medical wards. Interviewer administered questionnaire, anthropometric and spirometric measurements were done. RESULTS: Spirometry was performed in 720 acute admissio...

Dyspneic smokers who come to clinical attention demonstrate varying combinations of emphysema, airway inflammation, and fibrosis in addition to the changes of pulmonary Langerhans' cell histiocytosis. There is also growing acceptance of a link between cigarette smoke and alveolar wall fibrosis. Acute eosinophilic pneumonia is a dramatic response to recent-onset smoking seen in a small number of individuals. The interconnected pathways that lead to lung inflammation and fibrosis in cigarette smokers are slowly coming into focus. PMID:19935224

Full Text Available Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL expressing variant (smooth phenotype in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8 and human β-defensin 2 (HβD2 are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2 receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with "masking" of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system.

Background: There are very few studies are done on interstitial lungdiseases (ILD) in India. Methods: We conducted a retrospective study of 30 patients of high resolution computed tomography (HRCT) proven interstitial lungdiseases in tertiary care centre. Results: Most common etiological causes of ILD were occupational (46.62%), Rheumatoid Arthritis (13.32%), and idiopathic pulmonary fibrosis (33.33 %). Majority were in age group 40-49 years (mean age-45.23 years) and 66.5% male patients. C...

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lungdiseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. PMID:25959386

Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

Diffuse cystic lungdisease (DCLD) is a group of heterogeneous diseases that present as diffuse cystic changes in the lung on computed tomography of the chest. Most DCLD diseases are rare, although they might resemble common diseases such as emphysema and bronchiectasis. Main causes of DCLD include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, pulmonary Langerhans cell histiocytosis, lymphoid interstitial pneumonia, amyloidosis, light-chain deposition disease, Sjögren syndrome, and primary or metastatic neoplasm. We discuss clinical factors that are helpful in the differential diagnosis of DCLDsuch as sex and age, symptoms and signs, extrapulmonary presentations, cigarette smoking, and family history. Investigations for DCLD include high-resolution computed tomography, biochemical and histopathological studies, genetic tests, pulmonary function tests, and bronchoscopic and video-assisted thoracoscopic biopsies. A proposed diagnostic algorithm would enhance ease of diagnosing most cases of DCLD. PMID:27231867

Full Text Available More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lungdiseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lungdisease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lungdisease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication of this medication. The incidence of amiodarone-induced lungdisease is approximately 5-7%.

Lung transplantation is an established therapy for advanced lungdisease. Among the common disease indications for lung transplantation, patients with interstitial lungdisease, in particular, idiopathic pulmonary fibrosis (IPF), have the worst prognosis. Thus referral to a transplant center should ideally be realised at the time of diagnosis of usual interstitial pneumonitis (UIP), regardless of lung function, in order to carry out a through initial assessment and evaluation. PMID:26884220

Cystic lungdisease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lungdisease from other entities, such as cavitary lungdisease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lungdiseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and f...

The monitoring of lung involvement in patients with connective tissue diseases is central to optimal long-term management and is directed towards: (a) the detection of supervening lung involvement not present at presentation and (b) the identification of disease progression in established lungdisease. For both goals, accurate surveillance requires multi-disciplinary evaluation with the integration of symptomatic change, serial pulmonary function trends and imaging data. Evaluated in isolation, each of these monitoring domains has significant limitations. Symptomatic change may be confounded by a wide variety of systemic factors. Pulmonary function tests provide the most reliable data, but are limited by measurement variability, the heterogeneity of functional patterns and the confounding effects of non-pulmonary factors. Chest radiography is insensitive to change but may provide rapid confirmation of major disease progression or alert the clinician to respiratory co-morbidities. Although high-resolution computed tomography has a central role in assessing disease severity, it should be used very selectively as a monitoring tool due to the associated radiation burden. Ancillary tests include echocardiography and exercise testing to proactively identify cases of pulmonary hypertension and worsening of oxygenation. In summary, a multi-disciplinary approach is essential for the identification of disease progression and prompt treatment of comorbidities that severely impact on the morbidity and mortality of disease. PMID:26735151

Full Text Available Abstract Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lungdisease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lungdiseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1, p67phox (NCF2, p40phox (NCF4, p22phox (CYBA, gp91phox (CYBB, DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT in a cohort of 95 lungdisease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lungdisease.

Inhaled particulates which stimulate a 'delayed', cellular mode of alveolar clearance are excreted to the airways through lymphoid foci in the bronchial bifurcations. The anatomic relations and developing pathology of the tissues adjacent to these foci, including the divisions of accompanying arteries, were studied by serial sectioning and photomicrographic modelling of rat lungs. The changes are typical of classic 'delayed' inflammatory reactions and, in the rat, the fully developed stage is characterised by fibrinoid necrosis involving all three layers of the arterial wall in a linear lesion across the leading edge of the flow divider. An hypothesis was developed to relate the injury to pulsatile forces. Recent published findings indicate that similarly placed lesions, with species-specific changes in development, are universal in both cerebral and extra-cranial arterial forks of man and animals. Possible associations of the microvascular changes with human atherosclerosis and their further significance in pulmonary and systemic effects arising from industrial and environmental contaminants are explored. (author)

, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lungdiseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about...... this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association....

Mycobacterium abscessus is a rapidly growing mycobacterium that has been affecting people undergoing invasive procedures, such as videosurgery and mesotherapy. This bacterium has global distribution, being found in numerous niches. The frequency of published reports of infection by rapidly growing mycobacteria associated with tattooing procedures has increased in recent years. However, in Brazil there were no case reports of M. abscessus after tattooing in the literature until now. In this pa...

To assess the potential role of MR imaging in chronic infiltrative lungdisease (CILD) by comparison with high-resolution CT (HRCT). Twenty patients with proved CILD (six with UIP, six with sarcoidosis, two with extrinsic allergic alveolities [EAA], and six miscellaneous) underwent 1.5-T MR imaging and HRCT of the chest. Cardiac-gated T1 (TR, 800 msec; TE, 20 msec) and proton density and T2 (TR, 2,000 msec; TE, 30/80 msec) sequences were performed. The MR images were reviewed by two chest radiologists, and the findings were compared with the HRCT scans. HRCT was superior to MR imaging in the anatomic assessment of the lung parenchyma and in the demonstration of mild fibrosis. However, MR images provided greater contrast between areas of airspace opacification and normal lung than did MRCT. In two patients with UIP, two with sarcoidosis, and two with EAA, MR images demonstrated airspace opacification not readily apparent on CT scans. In the two patients with EAA, the EAA had initially been missed with HRCT. HRCT is superior to MR imaging in anatomic assessment of the lung. However, the increased contrast on MR images allows better assessment of the presence and extent of airspace opacification, which has been shown to reflect disease activity. MR imaging may play an important role in the assessment of disease activity and response to treatment in patients with CILD

The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lungdisease. Until recently, it was thought that the lungdiseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.

The present article is the first in a series that will review selected rare lungdiseases. The objective of this series is to promote a greater understanding and awareness of these unusual conditions among respirologists. Each article will begin with a case that serves as a focal point for a discussion of the pathophysiology and management of the particular condition. The first article is on lymphangioleiomyomatosis (LAM); subsequent articles will focus on pulmonary alveolar proteinosis, alpha-1-antitrypsin deficiency and primary ciliary dyskinesia. LAM is a rare, progressive and (without intervention) often fatal interstitial lungdisease that predominantly affects women of childbearing age. LAM is characterized by progressive interstitial infiltration of the lung by smooth muscle cells, resulting in diffuse cystic changes of the lung parenchyma. The molecular basis of this disorder has been delineated over the past five years and LAM is now known to be a consequence of mutations in the tuberous sclerosis genes. This knowledge, combined with advances in our understanding of the signalling pathways regulated by these genes, has given rise to potential molecular therapies that hold great promise for treating this devastating disease. PMID:17036091

An interstitial lungdisease (ILD) belongs to a group of diffuse parenchyma lungdiseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution...

During the course of certain inflammatory lungdiseases, SLPI (secretory leucoprotease inhibitor) plays a number of important roles. As a serine antiprotease it functions to protect the airways from proteolytic damage due to neutrophil and other immune cell-derived serine proteases. With respect to infection it has known antimicrobial and anti-viral properties that are likely to contribute to host defence. Another of its properties is the ability to control inflammation within the lung where it can interfere with the transcriptional induction of pro-inflammatory gene expression induced by NF-kappaB (nuclear factor kappaB). Thus, factors that regulate the expression of SLPI in the airways can impact on disease severity and outcome. Gender represents once such idiosyncratic factor. In females with CF (cystic fibrosis), it is now thought that circulating oestrogen contributes, in part, to the observed gender gap whereby females have worse disease and poorer prognosis than males. Conversely, in asthma, sufferers who are females have more frequent exacerbations at times of low-circulating oestrogen. In the present paper, we discuss how SLPI participates in these events and speculate on whether regulatory mechanisms such as post-transcriptional modulation by miRNAs (microRNAs) are important in the control of SLPI expression in inflammatory lungdisease.

Interstitial lungdiseases are a mixed group of diffuse parenchymal lungdiseases which can have an acute or chronic course. Idiopathic diseases and diseases with an underlying cause (e.g. collagen vascular diseases) share the same patterns. Thin section computed tomography (CT) plays a central role

The present article is the first in a series that will review selected rare lungdiseases. The objective of this series is to promote a greater understanding and awareness of these unusual conditions among respirologists. Each article will begin with a case that serves as a focal point for a discussion of the pathophysiology and management of the particular condition. The first article is on lymphangioleiomyomatosis (LAM); subsequent articles will focus on pulmonary alveolar proteinosis, alph...

Full Text Available Pulmonary hypertension (PH is a common complication of interstitial lungdiseases (ILDs, particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lungdiseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed “out-of-proportion” PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e. increased dyspnoea, low diffusion capacity and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs.

Abstract: Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a signifi cantly increased incidence of lung cancer and may infl uence treatment options and outcome. Impaired lung function confi rming COPD is an independent risk factor for lung cancer. Oxidative stress and infl ammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer developme...

The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lungdisease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lungdisease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lungdisease was discussed in several...

The interstitial lungdiseases affect the parenchyma of the lung including the pulmonary alveolar epithelium, the capillary endothelium and the spaces between these structures, together with the tissues within the septa including the perivascular and perilymphatic tissues. Although the different interstitial lungdiseases have rather similar clinical presentations with increasing shortness of breath, a restrictive lung function and a widespread shadowing on the chest radiograph, they comprise...

Accurate classification of interstitial lungdisease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD. PMID:26059704

Full Text Available The present article is the second in a series on rare lungdiseases. It focuses on pulmonary alveolar proteinosis (PAP, a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed.

In order to determine the significance of ground glass density on high-resolution CT scans of patients with idiopathic pulmonary fibrosis and other lung disorders, the authors have reviewed 200 high-resolution CT studies and found 50 cases demonstrating areas of hazy increased lung density. Disease entities most often associated with this finding included DIP, UIP, alveolar proteinosis, sarcoidosis, and bronchiolitis obliterans/ organizing pneumonia. Pathologic examination revealed either cellular or fluid material lining terminal air spaces, often associated with alveolar wall infiltration and an absence of fibrosis. Gallium scans and bronchoalveolar lavage in some cases showed active inflammation Follow-up high-resolution CT studies in 10 patients showed either change or resolution of the hazy densities, confirming the presence of a reversible parenchymal lesion

Mycobacterium abscessus is a rapidly growing mycobacterium that has been affecting people undergoing invasive procedures, such as videosurgery and mesotherapy. This bacterium has global distribution, being found in numerous niches. The frequency of published reports of infection by rapidly growing mycobacteria associated with tattooing procedures has increased in recent years. However, in Brazil there were no case reports of M. abscessus after tattooing in the literature until now. In this paper, we describe the case of a patient with a nine-month history of lesion on a tattoo site. The diagnosis of infection with Mycobacterium abscessus was established by correlation between dermatological and histopathological aspects, culture and molecular biology techniques. The patient had significant improvement of symptoms with the use of clarithromycin monotherapy. PMID:26560222

We report successful treatment of a case of Mycobacterium abscessus keratitis after laser in situ keratomileusis (LASIK) with therapeutic lamellar keratectomy. A 34-year-old woman developed a 2 x 2 mm feathery infiltration within the interface inferior to the pupil margin with mild inflammation of the conjunctiva in her left eye 40 days after LASIK surgery. Bacterial culture from the infiltrates of the interface of the stromal bed revealed Mycobacterium abscessus. After combination antibiotic therapy including amikacin and ciprofoxacin was given for 6 weeks, infiltration persisted despite the development of necrosis in the flap tissue. Therapeutic lamellar keratectomy combined with flap removal was performed. No recurrence was found 1 year after the surgery. Therapeutic lamellar keratectomy with flap removal can provide an effective treatment modality for the management of post-LASIK Mycobacterium abscessus keratitis that is unresponsive to medical treatment. PMID:14724729

Full Text Available Background: There are very few studies are done on interstitial lungdiseases (ILD in India. Methods: We conducted a retrospective study of 30 patients of high resolution computed tomography (HRCT proven interstitial lungdiseases in tertiary care centre. Results: Most common etiological causes of ILD were occupational (46.62%, Rheumatoid Arthritis (13.32%, and idiopathic pulmonary fibrosis (33.33 %. Majority were in age group 40-49 years (mean age-45.23 years and 66.5% male patients. Common symptoms were breathlessness on exertion (100%, dry cough (43.29%, anorexia (50% and joint pain (16.65%. Clubbing and bilateral crepitations were present in 50% and 63.27% of patients respectively. X- ray chest showed reticulo-nodular pattern (60%. Restrictive pattern (96.57% was present in majority patients in spirometry. Conclusion: Availability of non-invasive investigations like HRCT chest has increased our early recognitions of ILDs. Association of ILD in patients with autoimmune diseases must be ruled out. [National J of Med Res 2012; 2(1.000: 2-4

Full Text Available Abstract Diffuse parenchymal lungdiseases (DPLD represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases, the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood. Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice. This review focuses on idiopathic pulmonary fibrosis (IPF and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF.

Full Text Available The present article is the first in a series that will review selected rare lungdiseases. The objective of this series is to promote a greater understanding and awareness of these unusual conditions among respirologists. Each article will begin with a case that serves as a focal point for a discussion of the pathophysiology and management of the particular condition. The first article is on lymphangioleiomyomatosis (LAM; subsequent articles will focus on pulmonary alveolar proteinosis, alpha-1-antitrypsin deficiency and primary ciliary dyskinesia.

Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lungdisease. The purpose of this study was to describe the IPA patient with chronic lungdisease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lungdisease and 56 immunocompromised patients were compared. Patients with chronic lungdisease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lungdisease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lungdisease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lungdisease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lungdisease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lungdisease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lungdisease, have outcomes and mortality similar to that in the

Purpose: Accurate segmentation of lungs with severe interstitial lungdisease (ILD) in thoracic computed tomography (CT) is an important and difficult task in the development of computer-aided diagnosis (CAD) systems. Therefore, we developed in this study a texture analysis-based method for accurate segmentation of lungs with severe ILD in multidetector CT scans.

The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of c...

The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lungdisease alters these factors. Many forms of chronic lungdisease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lungdisease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

Despite advances in medical care, patients with cystic fibrosis still face limited life expectancy. The most common cause of death remains respiratory failure. End-stage cystic fibrosis can be treated with lung transplantation and is the third most common reason for which the procedure is performed. Outcomes for cystic fibrosis are better than most other lungdiseases, but remain limited (5-year survival 60%). For patients with advanced diseaselung transplantation appears to improve survival. Outcomes for patients with Burkholderia cepacia remain poor, although they are better for patients with certain genomovars. Controversy exists about Mycobacterium abscessus infection and appropriateness for transplant. More information is also becoming available for comorbidities, including diabetes and pulmonary hypertension among others. Extra-corporeal membrane oxygenation is used more frequently for end-stage disease as a bridge to lung transplantation and will likely be used more in the future. PMID:24655065

Although it appears very uncommon in adult COM, Mycobacterium abscessus should be considered as a possible cause of a chronically draining ear. Multi-antibiotic chemotherapy including high-dose clarithromycin can effectively treat adult COM cased by M. abscessus. The first case report of adult chronic otitis media (COM) caused by M. abscessus is described here. A 61-year-old woman presented persistent otorrhea for 2 months, despite treatment with standard antimicrobial drugs. Physical examination revealed a small perforation of the tympanic membrane and edematous middle ear mucosa. Mycobacterial cultures and PCR yielded non-tuberculous mycobacteria (NTM); M. abscessus. Intravenous panipenem/betamipron and amikacin and oral clarithromycin were administered for 36 days. Computed tomography of the temporal bone showed improved aeration in the tympanic cavity, but soft tissue shadow remained unchanged in the mastoid 31 days after starting medication. She therefore underwent tympano-mastoidectomy at 36 days. At surgery, inflammation remained in the middle ear, and edematous pale mucosal tissue was noted around the stapes and ossicular chain. Histopathologic examination showed inflammation and granulation tissue, but no caseating necrosis or acid-fast bacilli. After surgery the symptoms resolved and remained well without evidence of infection recurrence 12 months after the operation. PMID:20206453

The present review focuses on the interstitial lungdiseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lungdisease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed.

The present review focuses on the interstitial lungdiseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lungdisease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed

Full Text Available Background: Chronic granulomatous disease (CGD is an inherited phagocytes defect, characterized by defects of NADPH-oxidase and inability of bacterial killing, which leads to recurrent life-threatening infections. Respiratory problems, which are the major cause of morbidity in CGD, usually result from recurrent severe infections; however, vigorous inflammatory response could also cause respiratory diseases.Case Presentation: Herein, an 11 year-old patient with CGD is presented who suffered from chronic cough and dyspnea for 7 years. Considering the results of chest X-ray, high-resolution computed tomography, and pulmonary function test, the diagnosis of interstitial lungdisease was made.Conclusion: Early recognition of manifestations associated with CGD and appropriate treatment could prevent further complications and reduce morbidity and mortality in this group of patients.

Full Text Available Abstract Background The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism Mycobacterium smegmatis, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb. Results We have recently sequenced the complete genomes of two fast-growers causing human infections, Mycobacterium abscessus (CIP 104536T and M. chelonae (CIP 104535T. We show here that these two species contain genes corresponding to all those of the M. smegmatis "GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in M. chelonae and M. abscessus. One large cluster (19 genes comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (atf1 and atf2 in M. abscessus and M. chelonae has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (M. chelonae, 900 kb; M. abscessus, 3 Mb cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins. Conclusion Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in M. smegmatis represents the ancestral form and that evolution has scattered various pieces throughout the

Full Text Available BACKGROUND: Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lungdisease (DPLD, surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lungdisease. METHODS: A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist. RESULTS: Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2, cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lungdisease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25. The most frequent diagnosis was usual interstitial pneumonia (UIP (n = 7. Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications. CONCLUSION: In patients with suspected diffuse parenchymal lungdisease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield.

Full Text Available Idiopathic nontransplant-related childhood bronchiolitis obliterans is an uncommon disease. Most patients present with chronic recurrent dyspnea, cough and wheezing, which are also features of asthma, by far a much more common condition. The present case study reports on a six-year-old girl who presented to a tertiary care centre with recurrent episodes of respiratory distress on a background of baseline tachypnea, chronic hypoxemia and exertional dyspnea. Her past medical history revealed significant lungdisease in infancy, including respiratory syncytial virus bronchiolitis and repaired gastroesophageal reflux. She was treated for 'asthma exacerbations' throughout her early childhood years. Bronchiolitis obliterans was subsequently diagnosed with an open lung biopsy. She did not have sustained improvement with systemic corticosteroids, hydroxychloroquine or clarithromycin. Cardiac catheterization confirmed the presence of secondary pulmonary hypertension. Treatment options remain a dilemma for this patient because there is no known effective treatment for this condition, and the natural history is not well understood. The present case demonstrates the need for careful workup in 'atypical asthma', and the urgent need for further research into the rare lungdiseases of childhood.

Cystic fibrosis patients are highly susceptible to infections with non-tuberculous mycobacteria. Especially Mycobacterium abscessus infections are common but reliable diagnosis is hampered by non-specific clinical symptoms and insensitive mycobacterial culture. In the present study we established novel methods for rapid detection and immune characterization of Mycobacterium abscessus infection in cystic fibrosis patients. We performed Mycobacterium abscessus specific DNA-strip- and quantitati...

Lung epithelial ion transport promotes salt and water movement across the fetal and neonatal lung epithelium. The mechanism is dependent on basolateral membrane Na-K-ATPase and the apical membrane Cl(-) and Na(+) channels. During fetal life active secretion of Cl(-) and parallel movement of Na(+) across the epithelium into the developing lung lumen induce accumulation of liquid into the future airspaces. Postnatally, however, absorption of fluid from the airspaces must start. Present evidence suggests that activation of Na(+) transport from the lumen into the basolateral direction drives fluid absorption and results in an essentially dry air-filled alveolus. In laboratory animals amiloride, a Na(+) channel blocker, induces respiratory distress and impedes lung fluid clearance. One of the epithelial amiloride-sensitive Na(+) channels, ENaC, is composed of three homologous subunits that differentially respond to glucocorticoid hormone. In newborn infants an increase in pulmonary fluid and a defective Na(+) transport associate with respiratory distress. The ontogeny, subunit composition and function of ENaC along the respiratory tract are currently under investigation. It will be interesting to find out whether the subunit composition and function of lung ENaC respond to the therapy of the critically ill newborn infant. PMID:11359039

Aim: Interstitial lungdiseases are a heterogeneous group of diseases with a known or unknown etiology affecting the interstitium of the lung. In this study, our experience in the lung biopsy performed by video-assisted thoracoscopic surgery and open lung biopsy for interstitial lungdiseases is discussed. Material and Method: In this study, we reviewed 31 patients with a clinical diagnosis of interstitial lungdisease who underwent open or thoracoscopic lung biopsy between the years of 2004 ...

This article reviews major biomarkers in serum and bronchoalveolar lavage fluid (BALF) with respect to their diagnostic and prognostic value in connective tissue disease-associated interstitial lungdisease (CTD-ILD). In some CTD such as systemic sclerosis (SSc), the incidence of ILD is up to two-third of patients, and currently ILD represents the leading cause of death in SSc. Because of the extremely variable incidence and outcome of ILD in CTD, progress in the discovery and validation of biomarkers for diagnosis, prognosis, patients' subtyping, response to treatment, or as surrogate endpoints in clinical trials is extremely important. In contrast to idiopathic interstitial pneumonias, autoantibodies play a crucial role as biomarkers in CTD-ILD because their presence is strictly linked to the pathogenesis and tissue damage. Patterns of autoantibodies, for instance, anticitrullinated peptide antibodies in rheumatoid arthritis or aminoacyl-tRNA synthetases (ARS) in polymyositis/dermatomyositis, have been found to correlate with the presence and occasionally with the course of ILD in CTD. Besides autoantibodies, an increase in serum or BALF of a biomarker of pulmonary origin may be able to predict or reflect the development of fibrosis, the impairment of lung function, and ideally also the prognosis. Promising biomarkers are lung epithelium-derived proteins such as KL-6 (Krebs von den Lungen-6), SP-D (surfactant protein-D), SP-A (surfactant protein-A), YKL-40 (chitinase-3-like protein 1 [CHI3L1] or cytokines such as CCL18 [chemokine (C-C) motif ligand 18]). In the future, genetic/epigenetic markers, such as human leukocyte antigen (HLA) haplotypes, single nucleotide polymorphisms, and micro-RNA, may help to identify subtypes of patients with different needs of management and treatment strategies. PMID:24668534

IUATLD initiatives in non-tuberculous lungdisease developed in the late 1970s, coincident with improving tuberculosis control, and have targeted acute respiratory infections in children and chronic airways disease in adults and in children. The focus has been on methodology and the tools required to document the distribution and determinants of disease, and is illustrated in data gathered in African populations. Instruments developed include a simplified method of measuring bronchial hyper-reactivity and an asthma questionnaire Non-standard methods of questionnaire administration have also been validated, methods which are appropriate for use in the burgeoning urban communities and workforces of sub-Saharan Africa made up of rural migrants from different tribes and language groups. In addition, a review of reference values available for interpreting lung function in sub-Saharan African populations indicates a need to take into account a secular trend over the last two decades towards higher spirometric values. In the published data from Africa, not inconsiderable between-country differences are evident in the prevalence of chronic bronchitis in adults and of asthma in children. In addition, rates for childhood asthma were consistently higher in urban vs rural communities, with environmental factors playing an important role as well as being locally specific. Not only does the burden of morbidity attributable to both the chronic airway diseases reviewed justify past IUATLD initiatives in non-tuberculous lungdisease, but it also argues that future initiatives should focus on investigating between- and within-country differences using a standardized methodology, with a view to identifying local environmental determinants susceptible to intervention and control. Curbing tobacco use is clearly important, not only to benefit the health of adult smokers for whom the ill-health consequences have long been recognized, but, and more important, to protect the health of

Objective: To analysis the X-ray signs and subtype of the lung leptospira disease, and improve the undersdand, reduce the error diagnosis of this diseases. Methods: 40 cases of lung leptospira disease were evaluated about the check X-ray sings and clinical data, the check X-ray sings were dynamic observated and typed, and 40 cases had a diagnostic treatment. Results: There were various X-ray changes of lung leptospira disease. in 40 cases, 12 cases (30%) pulmonary marking, 21 cases (52%) little lesions, and 7 cases(18%) lager lesions, respectively. The patients who were correctly diagnosed made a recovery after effective treatment, the patients who were error diagnosed died because of multiple system organ damage. Conclusion: The check X-ray signs in lung leptospira disease have some characteristics. It may play an important role in improving this disease' diagnosis combining the dynamic observation of check X-ray sings with clinical data. (authors)

Full Text Available Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including the cystic fibrosis airway. Studies of the immune reaction to M. abscessus have focused primarily on macrophages and epithelial cells, but little is known regarding the neutrophil response despite the predominantly neutrophillic inflammation typical of these infections. In the current study, human neutrophils released less superoxide anion in response to M. abscessus than to Staphylococcus aureus, a pathogen that shares common sites of infection. Exposure to M. abscessus induced neutrophil-specific chemokine and proinflammatory cytokine genes. Although secretion of these protein products was confirmed, the quantity of cytokines released, and both the number and level of gene induction, was reduced compared to S. aureus. Neutrophils mediated killing of M. abscessus, but phagocytosis was reduced when compared to S. aureus, and extracellular DNA was detected in response to both bacteria, consistent with extracellular trap formation. In addition, M. abscessus did not alter cell death compared to unstimulated cells, while S. aureus enhanced necrosis and inhibited apoptosis. However, neutrophils augment M. abscessus biofilm formation. The response of neutrophils to M. abscessus suggests that the mycobacterium exploits neutrophil-rich settings to promote its survival and that the overall neutrophil response was reduced compared to S. aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy.

Full Text Available BACKGROUND: Interstitial lungdisease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lungdiseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lungdisease. METHODOLOGY/PRINCIPAL FINDINGS: Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lungdisease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology. CONCLUSIONS: These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lungdisease.

Radiological cross-sectional imaging modalities, particularly computed tomography (CT) have become the mainstays for diagnosing lungdisease in recent years. These enable morphological visualization of pathological processes with the greatest possible spatial resolution. Modern technical developments and complementary strategies have led to new applications and new functional assessments which need to be reviewed together with state-of-the-art techniques in nuclear imaging. The diagnosis of pulmonary embolism using spiral CT angiography and magnetic resonance (MR) angiography certainly belongs in this category. CT has become the an alternative modality of first choice, and it is also challenging pulmonary angiography as the gold standard. Direct visualization of patent pulmonary arteries and thromboembolic material is complemented by that of effects on the pulmonary parenchyma and right heart function; it also provides perfusion studies and MR-based flow measurement to assess hemodynamic compromise. Ventilation studies have long been a domain of nuclear imaging, and new techniques for the direct visualization of ventilation are emerging from recent developments in the field of MR imaging, for example, using hyperpolarized inert gases. New functional parameters of ventilation can be derived from these studies. For the diagnosis of metabolically active disease, such as tumor and pneumonia, CT offers very high sensitivity, for example, in screening for intrapulmonary nodules using low-dose CT and in the early detection of pulmonary infiltrates in high-risk patients. Especially for characterizing pulmonary nodules there is a need to combine nuclear medicine techniques, such as in positron-emission tomography. (orig.) [German] Die radiologischen Schnittbildverfahren, insbesondere die CT, haben sich innerhalb kurzer Zeit einen herausragenden Stellenwert in der Diagnostik von Lungenerkrankungen erworben. Dies umfasst in erster Linie die morphologische Darstellung

Full Text Available Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lungdisease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lungdisease (RA-ILD is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

The highly pulmonary concentration of 1,2-dipalmitoyl-sn-glycerol-3-phosphorylcholine (dipalmitoyllecithin) and its implication as an important component of lung surfactant have promoted investigation of phospholipid metabolism in the lung. This review will set the contents including recent informations for better understanding of phospholipid metabolism of the lung in normal state (physiological significances of lung phospholipids, characteristics of phospholipids in lung tissue and alveolar washing, biosynthetic pathways of dipalmitoyllecithin, etc.) as well as in toxic states (pulmonary oxygen toxicity, etc.) and in diseased states (idiopathic respiratory distress syndrome, pulmonary alveolar proteinosis, etc.) Since our main concern has been to clarify the most important route for supplying dipalmitoyllecithin, this review will be focused upon the various biosynthetic pathways leading to the formation of different molecular species of lecithin and their potential significance in the normal, toxic, and diseasedlungs.

Childhood Interstitial lungdisease (chILD) is an umbrella term used to define a broad range of rare, diffuse pulmonary disorders with altered interstitial structure that leads to abnormal gas exchange. Presentation of chILD in infancy can be difficult to differentiate from other common causes of diffuse lungdisease. This article aimed at paediatricians provides an overview of interstitial lungdisease presenting in infancy and includes key clinical features, a suggested approach to investigation and a summary of management. An overview of three clinical cases has been included to demonstrate the diagnostic approach, characteristic investigation findings and varied clinical outcomes. PMID:27145498

Pulmonary hypertension that develops in the setting of underlying lungdiseases such as COPD or idiopathic pulmonary fibrosis (IPF) is associated with decreased functional status, worsening hypoxemia and quality of life, and increased mortality. This complication of lungdisease is complex in its origin and carries a unique set of diagnostic and therapeutic issues. This review attempts to provide an overview of mechanisms associated with the onset of pulmonary hypertension in COPD and IPF, touches on appropriate evaluation, and reviews the state of knowledge on treating pulmonary hypertension related to underlying lungdisease. PMID:27086030

systematically performed in clinical practice. Given the large number of patients with chronic lungdisease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific...... treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lungdisease related PH. Studies investigating existing PAH drugs in animal models of lungdisease related PH have indicated a positive effect, and so have case reports and open label studies. However...

Significance: Fetal lung development takes place in hypoxia meaning that premature birth is hyperoxia for the prematurely born infant. The most common respiratory morbidity afflicting premature infants is bronchopulmonary dysplasia (BPD). Pathophysiologically, BPD represents the impact of injury, including O2 toxicity, to the immature developing lung that causes arrested lung development. Recent Advances: The thioredoxin (Trx) system, which is predominantly expressed in pulmonary epithelia in...

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lungdisease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09{+-}1.28 for the normal subjects, 1.97{+-}0.89 for the patients with lungdisease, and 1.59{+-}0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lungdisease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (>20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lungdisease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lungdisease and valvular heart disease. (author)

Respiratory bronchiolitis-associated interstitial lungdisease (RB-ILD) designates interstitial lung changes in smokers, characterized histologically by bronchiolocentric accumulation of pigmented alveolar macrophages and fibrotic or cellular inflammatory changes of pulmonary interstitium. The definition is nearly identical to that of condensate pneumopathy, smoker's pneumopathy or smoker's lung, defined by accumulation of pigmented alveolar macrophages with bland alveoloseptal or peribronchial fibrosis and cellular inflammation of the bronchial wall. In addition to respiratory bronchiolitis, which is found in nearly all smokers, RB-ILD comprises a broad spectrum of varying degrees of the interstitial reaction to the exogenous injury of inhalation smoking with gradual transition to desquamative interstitial pneumonia (DIP). In most cases RB-ILD manifestations are subclinical and detected coincidentally. Radiographic features are reticulonodular and ground glass opacities of the lung. The high resolution computed tomography reveals centrilobular nodules, ground glass opacities, thickening of bronchial walls, and in some cases a reticular pattern. Mild emphysema is frequent. Lung function analysis reveals only minor restrictive or obstructive defects in most cases, often combined with hyperinflation. CO diffusing capacity is slightly to moderately impaired. Pronounced interstitial lungdiseases with serious restrictive defects and arterial hypoxemia have been reported infrequently. In differential diagnosis smoking related interstitial lungdiseases (DIP, Langerhans cell histiocytosis, idiopathic pulmonary fibrosis) and other interstitial lungdiseases have to be excluded. In most cases diagnosis can be achieved by bronchoalveolar lavage and transbronchial lung biopsy. In cases of pronounced interstitial lungdisease or assumption of an additional interstitial lungdisease besides RB-ILD a thoracoscopic or open lung biopsy can be necessary. RB-ILD has a favourable

Magnetic resonance imaging (MRI) of the lung has progressed tremendously in recent years. Because of improvements in speed and image quality, MRI is now ready for routine clinical use. The main advantage of MRI of the lung is its unique combination of structural and functional assessment in a single imaging session. We review the three major clinical indications for MRI of the lung: staging of lung tumors; evaluation of pulmonary vascular disease; and investigation of pulmonary abnormalities in patients who should not be exposed to radiation. (author)

Non-tuberculous mycobacterial skin infections have an increasing incidence. In immunocompetent patients, they usually follow local trauma. We present a case of cutaneous Mycobacterium abscessus infection following mesotherapy. The lesions were successfully treated with a combination of clarithromycin, ciprofloxacin, and doxycycline. Atypical mycobacterial infection should be suspected in patients who develop late-onset skin and soft tissue infection after cutaneous injury, injection, and surgical intervention, particularly if they do not respond to conventional antibiotic treatment. PMID:21487459

Non-tuberculous mycobacterial skin infections have an increasing incidence. In immunocompetent patients, they usually follow local trauma. We present a case of cutaneous Mycobacterium abscessus infection following mesotherapy. The lesions were successfully treated with a combination of clarithromycin, ciprofloxacin, and doxycycline. Atypical mycobacterial infection should be suspected in patients who develop late-onset skin and soft tissue infection after cutaneous injury, injection, and surg...

The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lungdisease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lungdiseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lungdisease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P<0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P<0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lungdisease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lungdisease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin. (orig.)

@@ Chronic inflammatory lungdisease is a common health problem and often treated with potent antibiotics, anti-tuberculosis drugs, and antifungal agents. However, in case of medical therapy failure, surgical treatment has been often considered as an effective procedure.

In spite of substantial advances in defining the immunobiology and function of structural cells in lungdiseases there is still insufficient knowledge to develop fundamentally new classes of drugs to treat many lungdiseases. For example, there is compelling need for new therapeutic approaches to address severe persistent asthma that is insensitive to inhaled corticosteroids. Although the prevalence of steroid-resistant asthma is 5–10%, severe asthmatics require a disproportionate level of he...

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society. These obstructive lungdiseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice...

The most important smoking-related interstitial lungdiseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lungdisease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emph...

Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela. PMID:26441024

Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970. The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population. The pertinent clinical data from these patients are described and compared to 28 additional patients reported from other institutions. Small-cell lung cancer represented the predominant histologic type of lung cancer encountered in both smoking and nonsmoking patients with HD, accounting for 42% of cases overall and greater than 55% of cases reported in reviews of second malignancies. Tobacco use was noted in only 53% of patients. Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD. Nineteen (68%) of these patients received subsequent chemotherapy salvage. The median age at diagnosis of HD and lung cancer was 39 and 45 years, respectively. The interval between diagnosis of HD and metachronous lung cancer averaged seven years but appeared to vary inversely with age. HD patients treated with supradiaphragmatic irradiation or combined modality therapy may be at increased risk for developing lung cancer. The high frequency of in-field malignancies that the authors observed and the prevalence of small-cell lung cancer in both smoking and nonsmoking patients suggests that chest irradiation may influence the development of metachronous lung cancer in these patients. The finding of a mean latent interval in excess of seven years emphasizes the need for close long-term observation

Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD

Full Text Available Chronic obstructive pulmonary disease (COPD and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

The purpose of the present review is to summarize the current knowledge on PH in relation to COPD and ILD from a clinical perspective with emphasis on diagnosis, biomarkers, prevalence, impact, treatment, and practical implications. PH in COPD and ILD is associated with a poor prognosis, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lungdisease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which is not systematically performed in clinical practice. Given the large number of patients with chronic lungdisease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lungdisease related PH. Studies investigating existing PAH drugs in animal models of lungdisease related PH have indicated a positive effect, and so have case reports and open label studies. However, treatment with systemically administered pulmonary vasodilators implies the risk of worsening the ventilation-perfusion mismatch in patients with lungdisease. Inhaled vasodilators may be better suited for PH in lungdisease, but new treatment modalities are also required. PMID:23849967

Multiple isolates of Mycobacterium abscessus subsp. bolletii, collectively called BRA100, were associated with outbreaks of postsurgical skin infections across various regions of Brazil from 2003 to 2009. We announce the draft genome sequence of a newly sequenced BRA100 strain, M. abscessus subsp. bolletii CRM-0020, isolated from a patient in Rio de Janeiro, Brazil.

People are exposed to hundreds of substances daily, some of which may induce pulmonary injury. Occupational LungDisease diagnosis requires 4 elements: Exposure to the harmful agent, adequate latency between exposure and beginning of the symptoms, syndrome with post-exposure abnormalities, and exclusion of other conditions which may otherwise explain signs and symptoms. Several occupational lungdisease classifications based on structural or functional injury, type of agent, or both have been proposed. Generally, 5 groups are considered: Pneumoconiosis, hypersensitivity pneumonitis, toxic fumes exposure, asthma, and occupational lung infections. Conventional radiographs and in specific situations, CT, are crucial elements for the diagnosis of Occupational LungDisease. In the patient with respiratory symptoms and altered imaging studies, the possibility of Occupational LungDisease should be considered. Radiologist should be familiar the variety of substances that cause these entities and their radiological features. In this article Occupational Lungdiseases are reviewed, including diagnostic criteria, classification, physiopathology, clinical and radiological manifestations as well as their corresponding histopathological features.

Full Text Available Objective. The phenomenon of pendelluft was described over five decades ago. In patients with regional variations in resistance and elastance, gas moves at the beginning of inspiration out of some alveoli into others. Gas moves in the opposite direction at the end of inspiration. The objective of this study was to apply the method of lung sounds mapping, which is known to provide regional information about gas flow, to study pendelluft in COPD patients. Methods. A 16-channel lung sound analyzer was used to collect sounds from patients with COPD (n=90 and age-matched normals (n=90. Pendelluft at the beginning of inspiration is expected to result in vesicular sounds leading the tracheal sound by a few milliseconds. Pendelluft at the end of inspiration is expected to result in vesicular sounds lagging the tracheal sound. These lead and lag times were calculated for the 14 chest wall sites. Results. The lead time was significantly longer in COPD patients: 123±107 ms versus 48±59 ms in controls (P<0.0001. The lag time was also significantly longer in COPD patients: 269±249 ms in COPD patients versus 147±124 ms in controls (P<0.0001. When normalized by the duration of the inspiration at the trachea, the lead was 14±13% for COPD versus 4±5% for controls (P<0.0001. The lag was 28±25% for COPD versus 13±12% for controls (P<0.0001. Both lead and lag correlated moderately with the GOLD stage (correlation coefficient 0.43. Conclusion. Increased lead and lag times in COPD patients are consistent with the phenomenon of pendelluft as has been observed by other methods.

Interstitial lungdiseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lungdisease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lungdisease. PMID:10444954

Training is defined as systematic physical activity in order to improve the physical working capacity, which causes measurable morphological and functional changes in organs. Effects and the rules of applying aerobic endurance training in patients with chronic diseases of the lungs are dealt with. Training does not replace the normal medication, but is an additional therapeutic mean in order to regain physical working capacity, lost by chronic immobilization in the natural course of disease. Contraindications are acute diseases and exacerbations, but not a certain degree of the disease. Training does not improve the lung function, but the function of the other organs, the physical working capacity ist based on (circulation, musculature). This helps to use optimally the remaining reserves of lung function. Methods of aerobic endurance training are described, the definition of aims, performance diagnostic and the finding of the exact doses of training according to intensity, duration, frequency and the weekly netto training time. The training in different diseases of the lungs is discussed: In asthma bronchiale the prophylaxis of the exercise induced asthma and permitted and forbidden drugs for asthmatics according to the rules of international olympic committee. In chronic bronchitis with arterial hypoxemia, in restrictive lungdiseases and in pulmonary hypertension. At last the way to prescribing training for patients with chronic pulmonary diseases is described as well as the advising of patients wishing to do sport by their own motivation or planning projects, for instance touristic ones, which require physical stress. PMID:8465532

We studied clinical and radiographic features of interstitial lungdisease (ILD) during trimethoprim/sulfamethoxazole (TMP/SMX) administration. Ten patients who had received prednisolone treatment for underlying diffuse pulmonary disease showed various ILDs after introduction of TMP/SMX. The radiographic features of the ILDs were not consistent with infectious disease or exacerbation of the underlying disease, and these diagnoses were excluded radiographically and on clinical grounds during t...

Full Text Available Diffuse parenchyma lungdisease (DPLD encompasses a hetero - geneous group of disorders, characterized by a spectrum of inflammatory and fibrotic changes affecting alveolar walls and air spaces. They comprise over 200 entities and include a wide spectrum of diseases, many uncommon and many of unknown etiology. The incidence and prevalence rates of DPLD have not been precisely estimated due to difficulties in ascertaining a specific diagnosis on a specific disease. MATERIAL & METHODS : Prospective observational study done on 20 adult patients with radiologically diffuse parenchymal lungdisease admitted between January 2010 and May 2015 in Govt. General & Chest Hospital, Hyderabad were subjected for Transbronchial Lung Biopsy via flexible fibreoptic bronchoscopy, without fluoroscopic guidance. RESULTS : Out of 20 patients studied adequate lung tissue was obtained in 15 patients, yield of the procedure was 75%. Out of 15 patient’s histopathological diagnosis of chronic interstitial pneumonia is seen in 5 members, interstitial fibrosis is seen in 4 members, non caseating granulomas seen in 4 members, pulmonary alveolar protenosis was seen in 1 member and normal lung histopathology was seen in 1 members. Diagnostic yield of the procedure was 93.3% and overall diagnostic yield was 70%. Two patients developed post procedure pneumothorax. Both of them underwent closed - tube thoracostomy, lung expanded well and ICD was removed in 4 days. No significant bleeding was observed in any patient. No mortality was observed after the procedure . CONCLUSIONS : Transbronchial lung biopsy through flexible bronchoscopy is a simple, safe and effective procedure for the diagnosis of diffuse parenchymal lungdiseases. Complications were observed in only few patients out of twenty, which were successfully managed with ICD.

Lung scintigraphy provides quantitative information about regional imbalances of pulmonary ventilation and blood flow, and may be used to characterize numerous states of pulmonary dysfunction. In this chapter, applications of ventilation-perfusion (V/Q) lung imaging to nonembolic lung disorders are addressed, as well as the principles underlying quantitative V/Q imaging. Because the principles related to xenon ventilation imaging are closely related to physiologic measurements of pulmonary ventilation, and because the relationship of xenon studies to ventilation physiology has been studied extensively, the initial sections of this chapter deal with the principles of xenon V/Q imaging. The chapter deals with newer tracers, such as Kr-81m and radiolabeled aerosols

Full Text Available Neutrophil extracellular traps (NETs are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including many lungdiseases. Most of the inflammatory lungdiseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis, acute lung injury, allergic asthma and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified; these NETotic pathways are dependent on the types of stimuli. All of these pathways however appear to result in the formation of NETs with DNA, modified extracellular histones, proteases and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to the host tissue. Innate immune collectins such as pulmonary surfactant protein D (SP-D binds NETs, and enhances the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lungdiseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase inhibitors, peptidylarginine deiminase-4 inhibitors and anti-histone antibodies. Too much of the good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amounts of NETs that accumulate in the tissues are essential for harnessing the power of NETs with minimal damage to the hosts.

Magnetic resonance imaging (MRI) of the lungs is becoming increasingly appreciated as a third diagnostic imaging modality besides chest x-ray and computed tomography (CT). Its value is well acknowledged for pediatric patients or for scientific use particularly when radiation exposure should be strictly avoided. However, the diagnosis of interstitial lungdisease is the biggest challenge of all indications. The objective of this article is a summary of the current state of the art for diagnostic MRI of interstitial lungdiseases. This article reflects the results of a current search of the literature and discusses them against the background of the authors own experience with lung MRI. Due to its lower spatial resolution and a higher susceptibility to artefacts MRI does not achieve the sensitivity of CT for the detection of small details for pattern recognition (e.g. fine reticulation and micronodules) but larger details (e.g. coarse fibrosis and honeycombing) can be clearly visualized. Moreover, it could be shown that MRI has the capability to add clinically valuable information on regional lung function (e.g. ventilation, perfusion and mechanical properties) and inflammation with native signal and contrast dynamics. In its present state MRI can be used for comprehensive cardiopulmonary imaging in patients with sarcoidosis or for follow-up of lung fibrosis after initial correlation with CT. Far more indications are expected when the capabilities of MRI for the assessment of regional lung function and activity of inflammation can be transferred into robust protocols for clinical use. (orig.)

HRCT is an exceedingly powerful tool when brought to bear on selected patients with diffuse lungdisease. In many ways HRCT effectively bridges the gap between the gestalt impression of a chest radiograph and the detailed, but very local, information provided by lung biopsy specimens. In the diagnostic flow chart which takes a patient with dyspnoea and non-specific radiographic shadowing through many tests, and possibly on to lung biospy, there is now enough evidence to elevate HRCT to a prime position in the hierarchy of investigations. (orig./VHE)

Epithelial branching during the process of lung development results in the establishment of distinct functional zones, each of which is characterized by a unique cellular composition and repertoire of local progenitor cells. Significant new insights into cellular and molecular mechanisms of epithelial maintenance that provide insights into the pathophysiology of lungdisease have been made in recent years. This review focuses on the complex structure–function relationship in the airway epithe...

The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lungdiseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for...

Introduction Few cases of pulmonary toxicity related to epidermal growth factor receptor-targeted agents have been described. Case presentation We report a case of a 63-year-old white male with stage IV non-small cell lung cancer treated with erlotinib who developed a interstitial lungdisease. Conclusion Respiratory symptoms during treatment with erlotinib should alert clinicians to rule out pulmonary toxicity. Early erlotinib withdrawal and corticoid administration were successful.

Exposures in the workplace result in a diverse set of diseases ranging from the pneumoconiosis to other interstitial lungdiseases to acute lung injury. Physician awareness of the potential disease manifestations associated with specific exposures is important in defining these diseases and in preventing additional disease. Most occupational diseases mimic other forms of lungdisease, including pulmonary fibrosis, sarcoidosis, adult respiratory distress syndrome (ARDS), and bronchiolitis. A "sarcoidosis"-like syndrome, usually limited to the lungs, may result from exposure to bioaerosols and a number of metals. Exposure to beryllium in the workplace produces a granulomatous lungdisease clinically indistinguishable from sarcoidosis, chronic beryllium disease (CBD). Beryllium's ability to produce a beryllium-specific immune response is used in the beryllium lymphocyte proliferation tests to confirm a diagnosis of CBD and exclude sarcoidosis. Exposure to other metals must also be considered in the differential diagnosis of sarcoidosis. When an individual presents acutely with ARDS or acute lung injury, an acute inhalational exposure must be considered. Exposure to a number of irritant substances at high levels may cause a "chemical pneumonitis" or acute lung injury, depending on the solubility and physicochemical properties of the substance. Some of the most notable agents include nitrogen and sulfur oxides, phosgene, and smoke breakdown products. Ingestion of paraquat may also result in an ARDS syndrome, with pulmonary fibrosis eventually resulting. Bronchiolitis is a rare manifestation of inhalational exposures but must also be considered in the clinical evaluation of inhalational exposure. PMID:12362066

Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lungdisease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lungdiseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodes (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lungdisease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lungdisease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.

Lung involvement in Crohn's disease is not well characterized. We reviewed our experience with 11 lung biopsies (seven wedge and four transbronchial) from patients with Crohn's disease to study this association further. Negative cultures, special stains for organisms Gomori-methenamine-silver [GMS], acid fast), and polymerase chain reaction for (four cases) were required for inclusion. The group included five women and six men with a mean age of 47 years (range 13-84 years). A diagnosis of Crohn's disease preceded the lungdisease in nine patients. In two patients the diagnosis of Crohn's disease followed the diagnosis of their pulmonary disease 1 and 15 months later. Radiologically, eight patients had diffuse infiltrates, two had bilateral nodular infiltrates, and one had a mass. Chronic bronchiolitis with nonnecrotizing granulomatous inflammation was present in four patients, one of whom was taking mesalamine. Two patients had an acute bronchiolitis associated with a neutrophil-rich bronchopneumonia with suppuration and vague granulomatous features. One patient on mesalamine had cellular interstitial pneumonia with rare giant cells. Four patients demonstrated organizing pneumonia with focal granulomatous features, two of whom were taking mesalamine, and one of these two responded to infliximab (anti-tumor necrosis factor) monoclonal antibody therapy. Noninfectious pulmonary disease in patients with Crohn's disease has variable histologic appearances, including granulomatous inflammation and airway-centered disease resembling that seen in patients with ulcerative colitis. Drugs may contribute to pulmonary disease in some patients. PMID:12548168

Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lungdiseases including allergic diseases (such as asthma), chronic obstructive pulmonary ...

Smoking-related interstitial lungdiseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lungdisease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lungdiseases (SRILD) allows a more confident and specific diagnosis. (orig.)

Smoking-related interstitial lungdiseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lungdisease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lungdiseases (SRILD) allows a more confident and specific diagnosis. (orig.)

Outbreaks of infections by rapidly growing mycobacteria following invasive procedures, such as ophthalmological, laparoscopic, arthroscopic, plastic, and cardiac surgeries, mesotherapy, and vaccination, have been detected in Brazil since 1998. Members of the Mycobacterium chelonae-Mycobacterium abscessus group have caused most of these outbreaks. As part of an epidemiological investigation, the isolates were typed by pulsed-field gel electrophoresis (PFGE). In this project, we performed a large-scale comparison of PFGE profiles with the results of a recently developed multilocus sequence typing (MLST) scheme for M. abscessus. Ninety-three isolates were analyzed, with 40 M. abscessus subsp. abscessus isolates, 47 M. abscessus subsp. bolletii isolates, and six isolates with no assigned subspecies. Forty-five isolates were obtained during five outbreaks, and 48 were sporadic isolates that were not associated with outbreaks. For MLST, seven housekeeping genes (argH, cya, glpK, gnd, murC, pta, and purH) were sequenced, and each isolate was assigned a sequence type (ST) from the combination of obtained alleles. The PFGE patterns of DraI-digested DNA were compared with the MLST results. All isolates were analyzable by both methods. Isolates from monoclonal outbreaks showed unique STs and indistinguishable or very similar PFGE patterns. Thirty-three STs and 49 unique PFGE patterns were identified among the 93 isolates. The Simpson's index of diversity values for MLST and PFGE were 0.69 and 0.93, respectively, for M. abscessus subsp. abscessus and 0.96 and 0.97, respectively, for M. abscessus subsp. bolletii. In conclusion, the MLST scheme showed 100% typeability and grouped monoclonal outbreak isolates in agreement with PFGE, but it was less discriminative than PFGE for M. abscessus. PMID:24899019

Radiation-induced lungdisease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lungdisease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lungdisease, with subsequent improvement, is striking and has not been previously described in children. (orig.)

Radiation-induced lungdisease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lungdisease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lungdisease, with subsequent improvement, is striking and has not been previously described in children. (orig.)

The relatively rarely occurring nocardial disease is usually found as a complication in patients with neoplasms or immunosuppression. The pathogenesis of nocardial disease in man, its pathological-anatomical effects on various organs and the divenity of its clinical appearance will be discussed. An early definitive diagnosis, possible only by microbiological tests, is very important because of the high degree of lethality due to secondary hematogeneous spread of this disease. However, clinical symptoms and radiological findings together with certain aspects of patient history may give important diagnostic clues. Radiological signs of nocardial infection are demonstrated using several cases proven to have nocardial disease of the lung. Differentialdiagnostic criteria with respect to other infections and neoplastic diseases of the lung are given. (orig.)

Chronic lungdisease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lungdisease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lungdisease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lungdisease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure. PMID:25821112

Chronic interstitial lungdisease (ILD) in children is a heterogeneous group of rare lung disorders characterized by an inflammatory process of the alveolar wall and the pulmonary interstitium that induces gas exchange disorders. The diagnostic approach to an ILD involves three essential steps: recognizing the ILD, appreciating the impact, and identifying the cause. The spectrum of clinical findings depends to a large extent on age. In the newborn, the beginning is often abrupt (neonatal respiratory distress), whereas there is a more gradual onset in infants (failure to thrive, tachypnea, indrawing of the respiratory muscles). In older children, the onset is insidious and the diagnosis can only be made at an advanced stage of the disease. The diagnosis is based on noninvasive methods (clinical history, respiratory function tests, chest X-ray, and high-resolution CT scan) and invasive techniques (bronchoalveolar lavage, transbronchial biopsy, video-assisted thoracoscopic biopsy, and open lung biopsy). The treatment of interstitial lungdisease in children depends on the nature of the underlying pathology. The most common therapeutic approach involves the use of corticosteroids and immunosuppressive agents for their anti-inflammatory and antifibrotic effects. Children with ILD also need support therapy (oxygen therapy, nutritional support, treatment of pulmonary arterial hypertension, vaccination). Lung transplantation is discussed in patients with severe respiratory failure. PMID:27021883

Full Text Available In patients presenting with severe dyspnea, several diagnostic challenges arise in distinguishing the diagnosis of pneumothorax versus several other pulmonary etiologies like bullous lungdisease, pneumonia, interstitial lungdisease, and acute respiratory distress syndrome. Distinguishing between large pulmonary bullae and pneumothorax is of the utmost importance, as the acute management is very different. While multiple imaging modalities are available, plain radiographs may be inadequate to make the diagnosis and other advanced imaging may be difficult to obtain. Ultrasound has a very high specificity for pneumothorax. We present a case where a large pulmonary bleb mimics the lung point and therefore inaccurately suggests pneumothorax. [West J Emerg Med. 2015;16(3:447–449.

Mining production has accounted for around 50% of the gross industrial product in Mongolia since 1998. Dust-induced chronic bronchitis and pneumoconiosis currently account for the largest relative share (67.8%) of occupational diseases in Mongolia, and cases are increasing annually. In 1967-2004, medically diagnosed cases of occupational diseases in Mongolia numbered 7,600. Of these, 5,154 were confirmed cases of dust-induced chronic bronchitis and pneumoconiosis. Lungdiseases and other mining-sector health risks pose major challenges for Mongolia. Gold and coal mines, both formal and informal, contribute significantly to economic growth, but the prevalence of occupational lungdiseases is high and access to health care is limited. Rapid implementation of an effective national program of silicosis elimination and pneumoconiosis reduction is critical to ensure the health and safety of workers in this important sector of the Mongolian economy.

Interstitial lungdiseases (ILDs) are a diverse range of conditions affecting the lung interstitium. The prototypic ILD, idiopathic pulmonary fibrosis (IPF), is a chronic progressive fibrotic lungdisease with a median survival of only 3 years from the time of diagnosis. Recently significant progress has been made in both our understanding of the pathogenesis and of the therapeutic targeting of IPF. This culminated in the worldwide approval of the first antifibrotic therapies nintedanib and pirfenidone. While an important first step, patients continue to progress and better therapies are urgently required. The aim of this article is to highlight some of the recent advances that have been made in our understanding of genetics, disease classification, clinical trial design, and novel antifibrotic therapy in IPF. It discusses future priorities if we are to continue to increase the length and quality of life of patients with IPF, and considers possible approaches to translate the progress made in IPF to other progressive fibrotic lungdiseases where our understanding remains limited. PMID:27231869

Almost 40 million people currently live with dementia but this is estimated to double over the next 20 years; despite this, research identifying modifiable risk factors is scarce. There is increasing evidence that cognitive impairment is more frequent in those with chronic lungdisease than those without. Chronic obstructive pulmonary disease affects 210 million people, with cognitive impairment present in 60% of certain populations. Co-morbid cognitive dysfunction also appears to impact on i...

Pulmonary Langerhans’ cell histiocytosis (PLCH) is an unusual cystic lungdisease that is also characterized by extrapulmonary manifestations. The current review discusses the presenting features and relevant diagnostic testing and treatment options for PLCH in the context of a clinical case. While the focus of the present article is adult PLCH and its pulmonary manifestations, it is important for clinicians to distinguish the adult and pediatric forms of the disease, as well as to be alert f...

This paper reviews hypotheses about roles of angiogenesis in the pathogenesis of inflammatory disease in two organs, the synovial joint and the lung. Neovascularisation is a fundamental process for growth and tissue repair after injury. Nevertheless, it may contribute to a variety of chronic inflammatory diseases, including rheumatoid arthritis, osteoarthritis, asthma, and pulmonary fibrosis. Inflammation can promote angiogenesis, and new vessels may enhance tissue inflammation. Angiogenesis ...

A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lungdisease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lungdisease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. PMID:25398579

Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lungdisease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lungdiseases. PMID:12524461

The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lungdiseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses--for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lungdisease. PMID:9337837

Drug-induced lungdiseases are an increasingly frequent cause of morbidity. Over 350 drugs are now recognized as being implicated in drug-induced lungdiseases. Early diagnosis is critical. Discontinuing the drug may result in regression of the adverse effect. Diagnosis is based on a history of drug exposure with a temporal relationship between the introduction of the drug and the onset of symptoms, histologic evidence of lung damage and exclusion of other causes of lung injury. Unfortunately there is no specific test available. Histologic and radiologic findings are often non specific and diagnosis can be difficult. Drugs can cause a constellation of distinct patterns of respiratory involvement and all anatomic compartments of the lungs may be involved. The most common patterns are: non specific interstitial pneumonia and fibrosis, pulmonary eosinophilia, hypersensitivity pneumonitis, pulmonary edema with or without diffuse alveolar damage, bronchiolitis obliterans organizing pneumonia, pulmonary hemorrhage and vasculitis. It is important to be familiar with their common radiologic appearances. PMID:16106793

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow imitation and pose a huge burden to society. These obstructive lungdiseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lungdiseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lungdisease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the currentstate

A 42-year-old woman presented with persistent cough, bloody sputum and fever. Her chest X-ray film showed an infiltrative shadow with cavitation in the upper lobe of the left lung. Acid-fast-bacilli were shown by sputum smear staining. The anti-tuberculosis drugs isoniazid, refampicin, ethambutol and pyrazinamide were prescribed, but her symptoms and chest X-ray findings did not improve. Findings of MTD and MAC-PCR were negative but Mycobacterium abscessus was confirmed by sputum culture with the DNA hybridization method. Combination therapy with clarithromycin, amikacin and imipenem/cilastatin for one month improved her symptoms and chest X-ray shadow, and clarithromycin monotherapy was carried out for another ten months. Drug susceptibility tests revealed this mycobacterium was sensitive to clarithromycin and amikacin. To determine the environmental factors related to this infection, several samples were examined. Acid-fast-bacilli were present in a smear from the bath room drain. However, to confirm the infectious routes, longer observation is needed. Moreover, serum amyloid protein A and ESR were useful markers to estimate the clinical course. PMID:17144576

The serum ferritin concentration has been determined by an immunoradiometric assay in 90 subjects with a variety of pulmonary diseases. No association between ferritin concentrations and finger clubbing has been found in any of the diseases studied. Ferritin levels were significantly raised in the subjects with bronchial carcinoma, but were not useful in monitoring recurrence of the tumour. Pulmonary artery and pulmonary vein ferritin concentrations were similar to systemic venous concentrati...

Mycobacterium abscessus is an acid-fast nontuberculous mycobacterium that grows rapidly in culture. The organism is found in dust, soil, and water and after trauma, it may infect skin and soft tissue. The organism is rarely found in humans, and infections occurring after cardiovascular surgery are rare clinical events. To our knowledge, only a few cases of hemodialysis arteriovenous graft infection and endocarditis caused by M. abscessus have been described. We reported a first case of patien...

Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lungdisease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lungdisease even in genotypes other than PI-ZZ. PMID:27296827

In this commentary, the pathogenesis of alveolitis is examined and elucidated by animal models. The use of broncho alveolar lavage (BAL) and Ga-67 citrate whole-body scanning as a measure of the activity of alveolar inflammation in workers is discussed. Gallium scan indices have been reported to be elevated in asbestosis, silicosis, and coal workers' pneumoconiosis; diseases which may now be evaluated at earlier, potentially reversible stages. Research in emphysema and other lungdiseases associated with α1 antitrypsin deficiency may help explain why coal miners develop focal emphysema. Furthermore, investigation of genetic factors may reveal why workers with similar exposures have a different susceptibility for the development of pneumoconiosis or lung cancer. Occupational asthma may not respond to removal of the worker from exposure because reactive airways may be a predisposing factor for chronic ashthma and chronic obstructive lungdisease. A continuing challenge will be disease risk in new industries such as electronics and alternate energy industries and new diseases in worker groups not previously studied, such as the variety of pneumoconioses among dental laboratory technicians who work with exotic metal alloys. 52 references

Full Text Available Lung Volume Reduction Surgery (LVRS has become an accepted modality for chronic pulmonary emphy-sema. Bilateral involve excision of emphysematous alveoli, which results in a 20% to 30% reduction in the volume of each lung. The goal of LVRS is to improve the respiratory mechanics in severe emphysema by re-expanding func-tional lung tissue that has been compressed by over-distended emphysematous alveoli, thus restoring diaphragmatic mobility and improving the bellows function of the chest wall structures. Anaesthesia for LVRS is a significant challenge to the anaesthetist as a result of high risk patient population and the nature of surgery. Management requires good understanding of the pathophysiology of the disease and surgical procedure. Close co-ordination be-tween the anaesthetist, surgeon and other support staff are of paramount importance.

Interstitial lungdiseases (ILDs) occur across the lifespan, from birth to advanced age. However, the causes, clinical manifestations, histopathology, and management of ILD differ greatly among infants, older children, and adults. The historical approach of classifying childhood ILD (chILD) using adult classification schemes may therefore have done more harm than good. Nevertheless, identification of novel forms of chILD in the past decade, such as surfactant metabolism dysfunction disorders and neuroendocrine cell hyperplasia of infancy (NEHI), as well as genomic analysis of adult ILDs, has taught us that identical genotypes may result in distinct phenotypes at different ages and developmental stages, and that lung developmental pathways and cellular phenotypes are often recapitulated in adult ILDs. Thus comparison of the pathophysiology of ILD in children and adults in the context of lung development is useful in understanding the pathogenesis of these disorders, and may lead to novel therapeutic interventions for ILDs at all ages. PMID:22087431

Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lungdiseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characteriza...

The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lungdiseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lungdisease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the

β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, an...

The Schneeberg lungdisease is the lung cancer, conditioned by radiation which is caused by the influence of radon and of its subsequent products. It has gained a great importance after World War II as a consequence of the intensified mining of uranium ore. From the history of the disease, lasting some centuries, the period of the twenties and thirties of this century is represented in which on one side the conception of the causal importance of radon has made its way little by little, and on the other side the disease was acknowledged as occupational disease within the first decree of occupational diseases in the former German Reich. Evaluating materials from Saxon archives it is described how the legislative preparations to the acknowledgement of the Schneeberg lungdisease as occupational disease and the simultaneous research to the elucidation of nature and cause of the disease have penetrated and influenced each other. (author)

Mycobacterial infections have caused enormous morbidity and mortality in people living with human immunodeficiency virus (HIV) infection. Of these, the most devastating has been tuberculosis (TB), the leading cause of death among HIV-positive persons globally. TB has killed more people living with HIV than any other infection. Diagnosis of latent TB infection (LTBI) is critical as treatment can prevent emergence of TB disease. Bacteriologic confirmation of TB disease should be sought whenever possible as well as drug susceptibility testing. When detected early, drug susceptible TB is curable. Similar to TB, nontuberculous mycobacteria (NTM) can also produce pulmonary and extrapulmonary infections including disseminated disease that can be fatal. Diagnosis through accurate identification of the pathogenic organism will greatly inform treatment. Depending on the NTM identified, treatment may not be curable. Ultimately, preventive strategies such as initiation of antiretroviral drugs and treatment of LTBI are interventions expected to have significant impacts on control of TB and NTM in the setting of HIV. This chapter will review the impact of pulmonary mycobacterial infections on HIV-positive individuals. PMID:26974300

The lung is a complex organ comprising multiple cell types that perform a variety of vital processes, including immune defense and gas exchange. Diseases of the lung, such as chronic obstructive pulmonary disease, asthma and lung cancer, together represent one of the largest causes of patient suffering and mortality. Logistical barriers that hamper access to embryonic, normal adult or diseasedlung tissue currently hinder the study of lungdisease. In vitro lung modeling represents an attractive and accessible avenue for investigating lung development, function and disease pathology, but accurately modeling the lung in vitro requires a system that recapitulates the structural features of the native lung. Organoids are stem cell-derived three-dimensional structures that are supported by an extracellular matrix and contain multiple cell types whose spatial arrangement and interactions mimic those of the native organ. Recently, organoids representative of the respiratory system have been generated from adult lung stem cells and human pluripotent stem cells. Ongoing studies are showing that organoids may be used to model human lung development, and can serve as a platform for interrogating the function of lung-related genes and signalling pathways. In a therapeutic context, organoids may be used for modeling lungdiseases, and as a platform for screening for drugs that alleviate respiratory disease. Here, we summarize the organoid-forming capacity of respiratory cells, current lung organoid technologies and their potential use in future therapeutic applications. PMID:26721435

The use of nanotechnology has significantly increased in different fields of science, including the development of drug delivery systems. Currently, the most modern pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions and polymeric nanoparticles, demonstrate extremely useful properties from the point of view of drug therapy. In this context, the development of nanocarriers for pulmonary application has been much debated by the scientific community in recent decades. Although research on the use of nanoparticles for pulmonary application are still in the initial phase, the studies conducted to date suggest that the development of drug delivery systems for systemic or local treatment of diseases that affect the respiratory system may be promising. (author)

Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lungdisease (COPD), and interstitial lungdisease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung. The intravenous infusion of MSCs, the common mode of delivery, is followed by their entrapment in lung vasculature before MSCs reach to other organ systems thus indicating the feasible and promising approach of MSCs therapy for lungdiseases. In this review, we discuss the mechanistic basis for MSCs therapy for asthma, ARDS, COPD, and ILD. PMID:23992090

The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with 81mKr, distribution of compliance in thoraco-pulmonary system (C) by 81mKr gas bolus inhalation method, perfusion study (Q) with 99mTc-MAA, 67Ga scintigraphy and an assessment of pulmonary epithelial permeability with 99mTc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO2 was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. 67Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of 67Ga. 67Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by 99mTc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author)

The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with {sup 81m}Kr, distribution of compliance in thoraco-pulmonary system (C) by {sup 81m}Kr gas bolus inhalation method, perfusion study (Q) with {sup 99m}Tc-MAA, {sup 67}Ga scintigraphy and an assessment of pulmonary epithelial permeability with {sup 99m}Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO{sub 2} was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. {sup 67}Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of {sup 67}Ga. {sup 67}Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by {sup 99m}Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author).

123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 64 patients with heart and lungdiseases. Distribution of MIBG in the chest was evaluated by planar images, using counts ratios of the heart to the mediastinum (H/M) and the unilateral lung to the mediastinum (Lu/M). Most of patients with heart diseases showed obvious lung uptake of MIBG. The ratios of H/M were 1.75±0.20 in the group without heart failure and 1.55±0.19 in the group with heart failure. The ratios of Lu/M in the right and left lung were 1.56±0.16 and 1.28±0.16 in the group without heart failure. And those were 1.45±0.16 and 1.19±0.15 in the group with heart failure. But 3 patients complicated with chronic pulmonary emphysema and one patient with interstitial pneumonia due to dermatomyositis showed markedly decreased lung uptake. The ratios of Lu/M in the right and left lung of these patients were 1.20, 1.17; 1.17, 1.13; 1.01, 0.97 and 1.27, 0.94, respectively. These results suggest that the lung uptake of MIBG may reflect the state of pulmonary endothelial cell function in clinical situations, considering that it has been demonstrated that MIBG may be useful as a marker of pulmonary endothelial cell function in the isolated rat lung. (author)

Full Text Available We report a case of an elderly woman who developed a severe, chronic pulmonary reaction to nitrofurantoin therapy that she had taken continuously for three years to prevent urinary tract infections. The patient was taking no other drug known to cause lungdisease but the diagnosis was delayed by failure to recognize the association between nitrofurantoin and adverse drug reactions affecting the lung. When originally seen, the patient was unable to care for herself due to dyspnea. Bronchoscopy with biopsy ruled out other causes of her pulmonary disease. Immediate withdrawal of nitrofurantoin led to substantial, sustained improvement and disappearance of symptoms over several months without administration of corticosteroids. Nitrofurantoin toxicity should always be considered in any person taking that drug who develops bilateral infiltrates.

Interstitial lungdiseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down ...

Interstitial lungdiseases (ILDs) occur across the lifespan, from birth to advanced age. However, the causes, clinical manifestations, histopathology, and management of ILD differ greatly among infants, older children, and adults. The historical approach of classifying childhood ILD (chILD) using adult classification schemes may therefore have done more harm than good. Nevertheless, identification of novel forms of chILD in the past decade, such as surfactant metabolism dysfunction disorders ...

Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lungdisease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lungdisease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lungdisease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD. PMID:23514215

Talcosis/ Talcpneumoconiosis is one of the rarer forms of magnesium silicate induced lungdisease, It usually occurs in the fourth decade and affects people working in talc related industries like roof, shingle, pharmaceutical companies, talcum powder industries, electric ceramics, rubber industry etc. We report a case of talc pneumoconiosis/talcosis in a 51yr old male who presented with breathlessness and dry cough for the past 5 yrs and progressively worsening for the past 5 days. Who was w...

Full Text Available An unusual case of pleuroparenchymal lungdisease caused by the inhalation of vermiculite dust, presumably containing asbestos fibers is described. The uniqueness of the case lies in the very indirect nature of exposure – the wife of a factory owner, rather than a worker exposed to asbestos, whose factory manufactured vermiculite. The present case illustrates the importance of taking careful occupational histories of all household members when presented with a patient whose chest radiograph exhibits features consistent with asbestos exposure.

Full Text Available Group 3 pulmonary hypertension (PH is a common complication of chronic lungdisease (CLD, including chronic obstructive pulmonary disease (COPD, interstitial lungdisease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.

Full Text Available Background: Lungdiseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lungdisease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001, arterial hypertension (OR = 1.95; P = 0.015, living related donor (OR = 2.69; P = 0.004, therapy for acute graft rejection (OR = 2.06; P = 0.038, immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011, azathioprine (OR = 2.25; P = 0.023, and tacrolimus (OR = 1.83; P = 0.041. The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001. Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lungdiseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation.

间质性肺疾病(ILD)患者中肺癌的发病率增高,特别是特发性肺纤维化合并肺癌的报道最多.ILD合并肺癌的病理类型以鳞状细胞癌最多,好发于肺下叶和外周部位.ILD的一些肿瘤标记物增高,与疾病的活动程度、严重程度、肺纤维化程度和病情预后等有关,并且具有一定的诊断价值.ILD的肿瘤标记物增高可能是其合并肺癌的危险因素.本文对ILD合并肺癌的流行病学研究和ILD的肿瘤标记物的研究进展做一综述.%A number of studies have shown a high incidence of lung cancer in patients with interstitial lungdisease (ILD),especially idiopathic pulmonary fibrosis.The most pathological type of ILD combined with lung cancer is squamous cell carcinoma,and it usually occurs in the lower lobes and peripheral parts.The increase of some tumor markers of ILD is associated with the degree of disease activity,severity,fibrosis,prognosis and so on,and it has a certain diagnostic value.The increase of ILD tumor markers may be the risk factors of ILD combined with lung cancer.This paper makes a review on the epidemiological study of ILD combined with lung cancer and the research progress of ILD tumor markers.

Lungdiseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lungdiseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lungdiseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lungdiseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lungdiseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lungdiseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lungdiseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lungdiseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lungdiseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lungdiseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lungdiseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lungdiseases that have been studied to a lesser extent. PMID:27200087

Mesenchymal stem cells (MSCs), a distinct population of adult stem cells, have amassed significant interest from both medical and scientific communities. An inherent multipotent differentiation potential offers a cell therapy option for various diseases, including those of the musculoskeletal, neuronal, cardiovascular and pulmonary systems. MSCs also secrete an array of paracrine factors implicated in the mitigation of pathological conditions through anti-inflammatory, anti-apoptotic and immunomodulatory mechanisms. The safety and efficacy of MSCs in human application have been confirmed through small- and large-scale clinical trials. However, achieving the optimal clinical benefit from MSC-mediated regenerative therapy approaches is entirely dependent upon adequate understanding of their healing/regeneration mechanisms and selection of appropriate clinical conditions. MSC-mediated acute alveolar injury repair. A cartoon depiction of an injured alveolus with associated inflammation and AEC apoptosis. Proposed routes of MSC delivery into injured alveoli could be by either intratracheal or intravenous routes, for instance. Following delivery a proposed mechanism of MSC action is to inhibit/reduce alveolar inflammation by abrogation of IL-1_-depenedent Tlymphocyte proliferation and suppression of TNF-_ secretion via macrophage activation following on from stimulation by MSC-secreted IL-1 receptor antagonist (IL-1RN). The inflammatory environment also stimulates MSC to secrete prostaglandin-E2 (PGE2) which can stimulate activated macrophages to secrete the anti-inflammatory cytokine IL-10. Inhibition of AEC apoptosis following injury can also be promoted via MSC stimulated up-regulation of the anti-apoptotic Bcl-2 gene. MSC-secreted KGF can stimulate AECII proliferation and migration propagating alveolar epithelial restitution. Alveolar structural engraftment of MSC is a rare event. PMID:22772131

Interstitial lungdisease (ILD) encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF) represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells). New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis. PMID:25726561

Genetic or environmentally-induced alterations in protein structure interfere with the correct folding, assembly and trafficking of proteins. In the lung the expression of misfolded proteins can induce a variety of pathogenetic effects. Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two major clinically relevant pulmonary disorders associated with protein misfolding. Both are genetic diseases the primary causes of which are expression of mutant alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) and SERPINA1, respectively. The most common and best studied mutant forms of CFTR and AAT are ΔF508 CFTR and the Glu342Lys mutant of AAT called ZAAT, respectively. Non-genetic mechanisms can also damage protein structure and induce protein misfolding in the lung. Cigarette-smoke contains oxidants and other factors that can modify a protein\\'s structure, and is one of the most significant environmental causes of protein damage within the lung. Herein we describe the mechanisms controlling the folding of wild type and mutant versions of CFTR and AAT proteins, and explore the consequences of cigarette-smoke-induced effects on the protein folding machinery in the lung.

Full Text Available Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and/or replace its composition. The signals that induce the recruitment of circulating monocytes to the injured lung, as well as their distinct gene expression profile and susceptibility to epigenetic reprogramming by the local environment remain unclear. In this review, we summarise the unique characteristics of the alveolar macrophage pool ontogeny, phenotypic heterogeneity and plasticity during homeostasis, tissue injury and normal ageing. We also discuss new evidence arising from recent studies where investigators described how the epigenetic landscape drives the specific gene expression profile of alveolar macrophages. Altogether, new analysis of macrophages by means of “omic” technologies will allow us to identify key pathways by which these cells contribute to the development and resolution of lungdisease in both mice and humans.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears ...

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with mode...

There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lungdisease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low- to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided. PMID:25945507

Rationale and Objectives: Lung cancer is a frequent cause of death among patients with chronic obstructive pulmonary disease (COPD). We examined whether the use of inhaled corticosteroids among patients with COPD was associated with a decreased risk of lung cancer.

Nanotechnology provides a broad range of opportunities to develop new solutions for clinical problems. For the pulmonary field, nanotechnology promises better delivery of drugs and nucleic acid-based therapeutics to disease sites. Administration of therapeutics via inhalation provides the opportunity for direct delivery to the lung epithelium, the lining of the respiratory tract. By appropriate selection of particle size, deep lung delivery can be obtained with control of phagocytic uptake, the removal of particles by resident macrophages. Nanotechnology can also help in pulmonary therapies administered by intravenous and oral routes through targeting specific cell types and controlling bioavailability and release kinetics. In the hematology field, nanotechnology can counter multiple drug resistance in leukemia by blocking drug efflux from cancer cells, and provide effective delivery of siRNA into lymphocytes to block apoptosis in sepsis. Controlling the surface properties of materials on devices such as valves and stents promises improved biocompatibility by inhibition of thrombosis, the formation of blood clots, and regulating cell adhesion and activation. Nanoparticle-based thrombolytic agents have the potential to improve the effectiveness of clot removal. Treatment of both lung and blood diseases is also likely to benefit from nano-scaffold-based methods for controlling the differentiation and proliferation of stem and progenitor cells. PMID:19331540

Full Text Available Interstitial lungdiseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down diagnostic probabilities. HRCT of the chest has emerged as an important tool in the evaluation of these disorders. Idiopathic Interstitial Pneumonias (IIP are a group of conditions which are classified into several types based on pathological features. Bronchoscopic procedures are helpful in diagnosis of certain disorders but are of limited value in classification of IIP which requires surgical biopsy. Usual Interstitial Pneumonia (UIP, also referred to as Idiopathic Pulmonary Fibrosis, has a progressive course and an unfavourable outcome. Certain new drugs have recently become available for treatment of UIP. Our approach towards diagnosis and management of interstitial lungdiseases based on personal experience over the past three decades is reported here. Key words: Usual interstitial pneumonia – sarcoidosis – pneumoconiosis – bronchoscopy – lung biopsy

markdownabstract__Abstract__ Cystic Fibrosis (CF) is a severe, life-shortening genetic disease with a wide spectrum of clinical manifestations, affecting 70,000 patients in the EU and USA. The most prevalent clinical manifestation is structural lungdisease. Structural lungdisease is the main cause of morbidity in CF and accounts for 85% of the deaths in CF patients (1). Important for the pathogenesis of structural lungdisease are genetic mutations on chromosome 7 encoding for the CF transm...

The natural resistance of Mycobacterium abscessus to most commonly available antibiotics seriously limits chemotherapeutic treatment options, which is particularly challenging for cystic fibrosis patients infected with this rapid-growing mycobacterium. New drugs with novel molecular targets are urgently needed against this emerging pathogen. However, the discovery of such new chemotypes has not been appropriately performed. Here, we demonstrate the utility of a phenotypic screen for bactericidal compounds against M. abscessus using a library of compounds previously validated for activity against M. tuberculosis. We identified a new piperidinol-based molecule, PIPD1, exhibiting potent activity against clinical M. abscessus strains in vitro and in infected macrophages. Treatment of infected zebrafish with PIPD1 correlated with increased embryo survival and decreased bacterial burden. Whole genome analysis of M. abscessus strains resistant to PIPD1 identified several mutations in MAB_4508, encoding a protein homologous to MmpL3. Biochemical analyses demonstrated that while de novo mycolic acid synthesis was unaffected, PIPD1 strongly inhibited the transport of trehalose monomycolate, thereby abrogating mycolylation of arabinogalactan. Mapping the mutations conferring resistance to PIPD1 on a MAB_4508 tridimensional homology model defined a potential PIPD1-binding pocket. Our data emphasize a yet unexploited chemical structure class against M. abscessus infections with promising translational development possibilities. PMID:27121350

Full Text Available Cystic Fibrosis (CF is the most common fatal monogenic disease among Caucasians. While CF affects multiple organ systems, the principle morbidity arises from progressive destruction of lung architecture due to chronic bacterial infection and inflammation. It is characterized by an innate immune defect that results in colonization of the airways with bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa from an early age. Within the airway microenvironment the innate immune cells including epithelial cells, neutrophils, and macrophages have all been implicated in the host defense defect. The neutrophil, however, is the principal effector cell facilitating bacterial killing, but also participates in lung damage. This is evidenced by a disproportionately elevated neutrophil burden in the airways and increased neutrophil products capable of tissue degradation, such as neutrophil elastase. The CF airways also contain an abundance of nuclear material that may be originating from neutrophils. Neutrophil extracellular traps (NETs are the product of a novel neutrophil death process that involves the expulsion of nuclear material embedded with histones, proteases, and antimicrobial proteins and peptides. NETs have been postulated to contribute to the bacterial killing capacity of neutrophils, however they also function as a source of proteases and other neutrophil products that may contribute to lung injury. Targeting nuclear material with inhaled DNase therapy improves lung function and reduces exacerbations in CF and some of these effects may be due to the degradation of NETs. We critically discuss the evidence for an antimicrobial function of NETs and their potential to cause lung damage and inflammation. We propose that CF animal models that recapitulate the human CF phenotype such as the CFTR−/− pig may be useful in further elucidating a role for NETs.

Full Text Available Background and Objectives: Bronchodilator reversibility and diurnal peak flow variability are considered characteristic of asthma patients. Patients with chronic obstructive pulmonary disease (COPD show poor reversibility. But reversibility and variability in other pulmonary diseases manifesting with airflow obstruction in not known. Therefore, we assessed reversibility and peak flow variability in patients with various lungdiseases to recognize the pattern. Materials and Methods : Seventy consecutive patients with a diagnosis of lungdiseases manifesting with airflow obstruction were recruited in the study. These included 23 patients with asthma, 11 patients with bronchiectasis, 16 patients with post-tubercular lungdisease (PTLD, and 20 patients with COPD. Ten healthy matched control subjects were also selected to pair with asthmatic patients. Bronchodilator reversibility test was done initially and peak expiratory flow rate (PEFR was measured for a duration of 1 week by patients themselves on a chart that was given to them. The mean amplitude percentage of these records were analyzed. Results : The mean values of peak flow variability were 14.73% ± 6.1% in asthmatic patients, 11.98% ± 7.5% in patients with bronchiectasis, and 10.54% ± 5.3% in PTLD. The difference in the mean values of peak flow variability between asthma and bronchiectasis, that is, 14.73 (6.1 vs 11.98 (7.5 was not statistically significant (P > 0.05. Forced expiratory volume one second (FEV 1 reversibility values were 14.77% ± 26.93%, 11.24% ± 20.43%, 10.85% ± 13.02%, 16.83% ± 22.84%, and 5.47% ± 4.99% in asthma, COPD, PTLD, bronchiectasis, and healthy subjects, respectively. Conclusion: Both reversibility and diurnal peak flow variability were higher in patients with various lungdiseases compared with normal healthy subjects. Although these are characteristic of asthma, some cases of bronchiectasis and PTLD patients may also manifest asthma-like PEFR variability

BACKGROUND: An atherosclerotic disease burden sufficient to put lung transplant candidates at risk for end-organ disease after transplantation is considered to be a relative contraindication for lung transplantation. OBJECTIVES: The aim of this study was to assess our current practice of cardiac workup by coronary angiography in lung transplant candidates ≥50 years of age. METHODS: We retrospectively analyzed 50 consecutive lung transplant candidates ≥50 years of age in which coronary a...

Full Text Available Systemic sclerosis sine scleroderma is a subtype of scleroderma, which is characterized by involvement of visceral organs, but no characteristic skin alteration. The involved organs could be kidneys, heart, gastrointestinal system, and lungs. Interstitial lungdisease (ILD is one of the pulmonary manifestations of sine scleroderma. We report a 38-year-old woman presenting with chill, fever, generalized malaise, dyspnea on exertion, and dry cough with a history of Raynaud′s phenomenon, who was evaluated by physical examination, spirometry, and computed tomography scan, that all lead to the diagnosis of ILD. Combination of high-titer positive anti-nuclear antibody, high erythrocyte sedimentation rate, positive C-reactive protein, and ILD could be explained by sine scleroderma.

Aerosol-based cell delivery technique via intratracheal is an effective route for delivering transplant cells directly into the lungs. An aerosol device known as the MicroSprayer(®) Aerosolizer is invented to transform liquid into an aerosol form, which then can be applied via intratracheal administration for drug delivery. The device produces a uniform and concentrated distribution of aerosolized liquid. Using the capability of MicroSprayer(®) Aerosolizer to transform liquid into aerosol form, our group has designed a novel method of cell delivery using an aerosol-based technique. We have successfully delivered skin-derived fibroblast cells and airway epithelial cells into the airway of a rabbit with minimum risk of cell loss and have uniformly distributed the cells into the airway. This chapter illustrates the application of aerosol device to deliver any type of cells for future treatment of lungdiseases. PMID:27062596

Full Text Available Talcosis/ Talcpneumoconiosis is one of the rarer forms of magnesium silicate induced lungdisease, It usually occurs in the fourth decade and affects people working in talc related industries like roof, shingle, pharmaceutical companies, talcum powder industries, electric ceramics, rubber industry etc. We report a case of talc pneumoconiosis/talcosis in a 51yr old male who presented with breathlessness and dry cough for the past 5 yrs and progressively worsening for the past 5 days. Who was working in a talcum powder manufacturing company for >28yrs in the packaging section. The diagnosis was possible by history, clinical examination, Chest X-ray, PFT/DLCO, HRCT chest, Bronchoscopy & Trans bronchial lung biopsy showing interstitial fibrosis.

Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lungdiseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. The best classification results were obtained by the MF features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers. The highest accuracy was found for MF.euler (97.5%, 96.6%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced topological texture features can provide superior classification performance in computer-assisted diagnosis of interstitial lungdiseases when compared to standard texture analysis methods.

Surgical lung biopsy, either open thoracotomy or video-assisted thoracoscopy is recommended in the diagnosis of interstitial lungdiseases (ILD). In some cases, however, the repetitive pattern of radiological features in high-resolution computed tomography is often sufficient to confirm the diagnosis in a non-invasive manner. The purpose of the study was to determine whether patients with ILD can be selected on the basis of the HRCT pattern. Thin-section CT scans were performed in 40 patients with histologically proven idiopathic interstitial pneumonia (26 patients with usual interstitial pneumonia UIP, 2 patients with desquamative interstitial pneumonia DIP, 2 patients with bronchiolitis obliterans organizing pneumonia BOOP, 2 patients with non-specific interstitial pneumonia NSIP, 11 patients with hypersensitivity pneumonitis, and 3 patients with pulmonary histiocytosis X). The location and the intensity of lesions were taken into consideration. Clinical and histopathological findings were compared. HRCT features of interstitial lungdiseases such as nodules and cystic spaces in hypersensitivity pneumonitis and pulmonary histiocytosis, and ground-glass opacities in idiopathic interstitial pneumonias (IIP) were statistically significant for differential diagnosis in ILD cases. Combination of honeycombing and ground-glass opacities found in UIP and nodules found in DIP were also statistically significant features in IIP subtypes diagnosis. In some cases, HRCT patterns of hypersensitivity pneumonitis, pulmonary histiocytosis X and IPF combined with clinical findings allowed for the accurate diagnosis without resorting to lung biopsy. Within a group of idiopathic interstitial pneumonia only in usual interstitial pneumonia characteristic pattern in thin-section CT can be defined. In other subgroups some typical features can imply a diagnosis. (author)

Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a "snapshot" in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lungdiseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lungdiseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and

Full Text Available Interstitial lungdisease (ILD is common in systemic sclerosis (SSc patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease. Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described. Nonselective immunosuppressors are still the main treatment for ILD, with cyclophosphamide (CYC most widely used to obtain remission. Novel therapies towards specific molecular and cellular targets have been suggested; in particular, rituximab (RTX has shown promising results, but further research is needed. It is of paramount importance to define the severity of the disease and the risk of progression in order to define the need for treatment and the treatment intensity. We propose the division of the treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation, medium intensity (CYC and RTX and low intensity (azathioprine (AZA and mycophenolate mofetil (MMF. After obtaining remission, maintenance treatment with AZA or MMF should be started. In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD.

Pulmonary surfactant is a highly surface-active mixture of proteins and lipids that is synthesized and secreted in the alveoli by type II epithelial cells and is found in the fluid lining the alveolar surface. The protein part of surfactant constitutes two hydrophilic proteins (SP-A and SP-D) that regulate surfactant metabolism and have immunologic functions, and two hydrophobic proteins (SP-B and SP-C), which play a direct role in the organization of the surfactant structure in the interphase and in the stabilization of the lipid layers during the respiratory cycle. Several studies have shown that cigarette smoke seems to affect, in several ways, both surfactant homeostasis and function. The alterations in surfactants' biophysical properties caused by cigarette smoking, contribute to the development of several smoking related lungdiseases. In this review we provide information on biochemical and physiological aspects of the pulmonary surfactant and on its possible association with the development of two major chronic diseases of the lung known to be related to smoking, i.e. chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Additional information on the possible role of surfactant protein alterations and/or dysfunction in the combination of these two conditions, recently described as combined pulmonary fibrosis and emphysema (CPFE) are also provided. PMID:26420367

Lungdiseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lungdiseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lungdiseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lungdiseases. PMID:23959715

BACKGROUND: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting. METHODS: Longitudinal registry study of 432 patients with cystic...... slower decline, similar in magnitude to the pre-infection slope. CONCLUSIONS: In a national population we have demonstrated the impact on lung function of each chronic CF pathogen. M. abscessus complex was associated with the worst impact on lung function. Eradication of M. abscessus complex may...

From 2006 to 2011, an outbreak of a particular type of childhood interstitial lungdisease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea. PMID:27134508

The frequency distributions of ventilation-perfusion (V-P) patterns in various lungdiseases were compared to those observed in pulmonary embolism in order to determine whether the V-P patterns for pulmonary embolism constituted a frequent finding in these disorders. The results showed that a segmental or labor perfusion defect with normal ventilation, was associated with a high probability of thromboembolic lungdisease, and was not present in any of the other lungdiseases studied. (orig.)

Endobronchial laser therapy was used in children with nonspecific lungdiseases. Effectiveness of laser therapy was evaluated by use of cytogram of bronchoalveolar lavage fluid (BALF). There was observation of 29 children with nonspecific lungdiseases: they had been performed endobronchial laser therapy with use of gallium arsenide laser. This investigation has proved the effectiveness of laser therapy, and the method is recommended for treatment of nonspecific lungdiseases in children.

Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the cont...

Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lungdisease. Recognition of occupational lungdisease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT) is superior...

Full Text Available Interstitial lungdisease (ILD is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc. Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed.

Background Interstitial lungdiseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell–activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. Methods We examined serum lev...

Full Text Available Interstitial lungdisease (ILD encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells. New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis.

Drug-induced interstitial lungdiseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.)

Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lungdiseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

The aim of this study was to assess if the chest radiograph appearance at seven days of age could be used to predict chronic lungdisease. 60 preterm infants who were ventilated and/or had supplementary oxygen at seven days of age and had a chest radiograph performed at that postnatal age, were prospectively recruited. These chest radiographs were scored according to lung volume, presence of opacification, haziness, interstitial changes and cystic elements. 28 infants subsequently developed chronic lungdisease; their median chest radiograph score was 5.5 which was significantly higher than that of the non-chronic lungdisease infants. A chest radiograph score of 4 had a 71% sensitivity and 88% specificity in predicting chronic lungdisease. It is concluded that chest radiograph appearance at seven days of age is a sensitive and specific predictor of chronic lungdisease and thus could be used to indicate the need for preventive therapy. 22 refs., 1 fig., 1 tab

Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/tyrosine kinase (EGFR) inhibitor which is used for non-small-cell lung cancer treatment. Despite that erlotinib is considered to have a favorable safety profile, adverse events such as interstitial lungdisease (ILD) were reported in pivotal studies. The authors report the first histologically confirmed case of fatal ILD associated with erlotinib therapy. The medical record of a patient who developed fatal ILD after receiving erlotinib treatment was reviewed to identify the cause of death and other factors potentially contributive to this adverse outcome. A 55-year-old smoker with no evidence of pre-existing interstitial disease developed bilateral ILD and respiratory failure which could be explained only as a toxicity of erlotinib. He had a history of stage IV left upper lobe squamous-cell carcinoma for which he had received three successive regimens of chemotherapy (ifosfamide plus gemcitabine, docetaxel, mitomycin plus navelbine), followed five months later by erlotinib. At initiation of erlotinib treatment there were no radiological signs suggestive of ILD disease or apparent clinical signs of respiratory distress. While the patient completed two months with erlotinib therapy he developed bilateral interstitial infiltrates; despite discontinuation of erlotinib he was admitted with respiratory failure two weeks later. Diagnostic work up for other causes of pneumonitis including infectious diseases, congestive cardiac failure and pulmonary infraction was negative. Empiric treatment with oxygene, corticosteroids and later with cyclophosphamide was ineffective and the patient progressively deteriorated and died. The clinical and post-mortem examination findings are presented and the possible association relationship between erlotinib induced ILD and previous chemotherapy is discussed. Physicians should be alert to the fact that erlotinib related ILD, although infrequent, is potential fatal. The

Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lungdisease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.

Sequential changes of interstitial lungdisease in fourteen patients of polymyositis/dermatomyositis (PM/DM) were followed up by high-resolution CT (HRCT). Most frequent CT findings were intense lung attenuation (ILA) with volume loss and slightly increased lung attenuation (SILA). Open lung biopsy was performed in a case with ILA shadow which revealed so-called usual interstitial pneumonia (UIP). Most intense ILA and SILA shadows resolved after steroid therapy. Some of ILA, however, reappeared and accompanied more prominent volume loss findings than before treatment. We think HRCT findings of interstitial lungdisease in PM/DM may indicate prognosis of these diagnoses to some degree. (author)

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lungdiseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

Full Text Available BACKGROUND: Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lungdiseases (f-DPLD when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. OBJECTIVES: To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. METHOD: Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT features. RESULTS: SAFETY: pneumothorax occurred in 19 patients (28%. One patient (1.4% died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%. The median size of cryobiopsies was 43.11 mm(2 (range, 11.94-76.25. Diagnostic yield: among adequate TBLC the pathologists were confident ("high confidence" that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%, including 36 of 47 with UIP (77% and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular, 2 desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lungdisease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident ("low confidence". Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69-0.97. Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63 of cases were classified as Idiopathic Pulmonary Fibrosis (IPF, 30% (19/63 as possible IPF, 25% (16/63 as other f-DPLDs and 13% (8/63 were unclassifiable. CONCLUSIONS: TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical

The occurrence of vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in the proximal and distal bronchi was studied in humans with tuberculosis and sarcoidosis by use of radioimmunoassay and immunohistochemically. Sample from patients shows chronic obstructive disease (COPD), and irradiated lungs are also examinated. There were no statistical difference in VIP and NPY concentrations between the different patient groups. However, in eleven cases from all three groups of patients (out of in total 40) high contents of VIP in both segmental and lobar bronchi was observed. It's interesting, all the samples from patients showing market allergic manifestations exhibited high VIP levels. The SP levels were observed to be low or even to be undetectable in tuberculosis disordered tissue. There were fewer neuropeptide - immunoreactive nerve fibres in the 'affected' than in 'unaffected' sides of tuberculosis patients. Conclusions: There appear to be changes in the innervation pattern in tuberculosis affected lungs tissue, but not in response to sarcoidosis. Allergic airways manifestations and seems to correlate to high VIP level in bronchi. (author)

To evaluate the abnormalities of bronchovascular bundles in the differential diagnosis of the diffuse lungdisease, seventy-two patients with diffuse lungdiseases were evaluated, 15 of 72 patients were pathologically proven and the others clinically proven. Of these 72 patients, there were 33 patients with diffuse pulmonary interstitial disease, 5 patients with pulmonary parenchymal disease, 14 patients with bronchial disease, and 20 patients with disseminated disease. All patients had conventional CT scan of the chest, some also had HRCT scan. All CT images were jointly reviewed by two radiologists. The features of the abnormalities of bronchovascular bundles included: (1) Thinning of bronchovascular bundles, predominantly seen in diffuse interstitial disease of lung and chronic bronchitis; (2) thickening of bronchovascular bundles, predominantly seen in interstitial diseases and disseminated lungdiseases such as sarcoidosis and lymphangitis carcinomatosis with beaded appearance of bronchovascular bundles; (3) Increased visibility of bronchovascular bundles, predominantly seen in bronchiolitis and disseminated lungdiseases. CT features of the abnormalities of bronchovascular bundles are present in 80% of diffuse lungdiseases. The features are not specific, but the beaded bronchovascular bundles are always seen in sarcoidosis and lymphangitis carcinomatosis. In making a distinction between idiopathic pulmonary fibrosis and chronic bronchitis complicated with interstitial fibrosis, the position of diaphragm is of value in differential diagnosis, normal or elevated diaphragm is usually seen in the former, while low and flattened diaphragm in the latter. Change of the appearance of bronchovascular bundles from normality to abnormality reflects the process of development of the lungdisease

There are myriad pulmonary conditions associated with HIV, ranging from acute infections to chronic noncommunicable diseases. The epidemiology of these diseases has changed significantly in the era of widespread antiretroviral therapy. Evaluation of the HIV-infected patient involves assessment of the severity of illness and a thorough yet efficient pursuit of definitive diagnosis, which may involve multiple etiologies simultaneously. Important clues to a diagnosis include medical and social history, demographic details such as travel and geography of residence, substance use, sexual practices, and domiciliary and incarceration status. CD4 cell count is a tremendously useful measure of immune function and risk for HIV-related diseases, and helps narrow down the differential. Careful history of current symptoms and physical examination with particular attention to extrapulmonary signs are crucial early steps. Many adjunctive laboratory studies can suggest or rule out particular diagnoses. Pulmonary function testing (PFT) may aid in characterization of several chronic noninfectious illnesses accelerated by HIV. Chest radiograph and computed tomography (CT) scan allow for classification of diseases by pathognomonic imaging patterns, although many infectious conditions present atypically, particularly with lower CD4 counts. Ultimately, definitive diagnosis with sputum, bronchoscopy with bronchoalveolar lavage, or lung tissue is often needed. It is of utmost importance to maintain a high degree of suspicion for HIV in otherwise undiagnosed patients, as the first presentation of HIV may be via an acute pulmonary illness. PMID:26974298

High resolution CT is now the method of choice in the diagnosis of lungdiseases, especially in their early recognition. However, the radiologist must be aware of precise anatomic, pathologic and physiologic data which are observed when the patient is supine. This concept leads to a transversal analysis of lungdiseases by CT, as previously proposed in the coronal and sagittal planes for conventional chest X Ray interpretation. The aim of the study is to demonstrate that these regional differences in the lung must be included in the method of chest scanning but also in the interpretation of lungdiseases

Background Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID) of the brain is protective against the development of brain metastases in lung cancer patients. Methodology/Principal Findings A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the ...

Mycobacterium abscessus is a nontuberculous mycobacterium that is increasingly recognized as an opportunistic pathogen in cystic fibrosis (CF) patients. Factors that predispose CF patients to infection by this environmental bacterium remain unknown. In a case-control study of 22 CF patients with M.

Full Text Available Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds.

In cystic fibrosis inhalation of drugs for the treatment of CF related lungdisease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lungdisease or are currently under development. In this European consensus document we...

In cystic fibrosis inhalation of drugs for the treatment of CF related lungdisease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lungdisease or are currently under development. In this European consensus document we revie

Full Text Available Cystic Fibrosis (CF lungdisease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lungdisease and the occurrence of pulmonary exacerbations (PEx are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lungdisease.54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lungdisease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001.Adults and children with moderate to severe CF lungdisease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency.MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lungdisease and PEx.

Background and aims Cystic Fibrosis (CF) lungdisease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lungdisease and the occurrence of pulmonary exacerbations (PEx) are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lungdisease. Methods 54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lungdisease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001. Results Adults and children with moderate to severe CF lungdisease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency. Conclusions MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lungdisease and PEx. PMID:25545245

We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lungdisease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan ...

Results demonstrate that proton MR signal changes among different lung volumes are in good agreement with 3He MR ventilation imaging findings and can be successfully applied in both healthy volunteers and patients with obstructive lungdisease.

value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (Ppersons with COPD......BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than...... population norms. METHODS: We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or value) at cohort inception (mean age of patients, approximately...

Full Text Available SUMMARY. Recent technological innovations have resulted in the introduction of new substances in different manufacturing procedures. Unfortunately, lack of knowledge of the adverse effects of some novel substances has led to the development of interstitial lungdisease (ILD among exposed workers. Exposure to diacetyl can cause bronchiolitis obliterans (“popcorn lung”, while exposure to nylon flock, Acramin-FWN, indium-tin oxide, biomass fuels or nanoparticles is associated with ILD. In addition, hypersensitivity pneumonitis can occur after exposure to additives in animal feed. Finally, new applications of substances already known to be hazardous can result in the occurrence of ILD in exposed workers. Pneumon 2010, 23(3:293-300.

Full Text Available Innate lymphoid cells (ILCs are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages.Three types of ILCs (ILC1, 2 & 3 have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK cells and interferon (IFN-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis.There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD. Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lungdiseases.In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD.

Full Text Available Interstitial lungdisease (ILD is a relevant extra-articular manifestation of rheumatoid arthritis (RA that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP; other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lungdisease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD. PMID:26757299

This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lungdisease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lungdisease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lungdisease. In addition, the progression of lungdisease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lungdisease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lungdisease. PMID:26405283

In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lungdiseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancer and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lungdiseases, and lung cancer risk for both the sexes.

Full Text Available Abstract Background Interstitial lungdisease encompasses a diverse group of chronic lung conditions characterised by distressing dyspnoea, fatigue, reduced exercise tolerance and poor health-related quality of life. Exercise training is one of the few treatments to induce positive changes in exercise tolerance and symptoms, however there is marked variability in response. The aetiology and severity of interstitial lungdisease may influence the response to treatment. The aims of this project are to establish the impact of exercise training across the range of disease severity and to identify whether there is an optimal time for patients with interstitial lungdisease to receive exercise training. Methods/Design One hundred and sixteen participants with interstitial lungdisease recruited from three tertiary institutions will be randomised to either an exercise training group (supervised exercise training twice weekly for eight weeks or a usual care group (weekly telephone support. The 6-minute walk distance, peripheral muscle strength, health-related quality of life, dyspnoea, anxiety and depression will be measured by a blinded assessor at baseline, immediately following the intervention and at six months following the intervention. The primary outcome will be change in 6-minute walk distance following the intervention, with planned subgroup analyses for participants with idiopathic pulmonary fibrosis, dust-related interstitial lungdisease and connective-tissue related interstitial lungdisease. The effects of disease severity on outcomes will be evaluated using important markers of disease severity and survival, such as forced vital capacity, carbon monoxide transfer factor and pulmonary hypertension. Discussion This trial will provide certainty regarding the role of exercise training in interstitial lungdisease and will identify at what time point within the disease process this treatment is most effective. The results from this study will

Chronic lungdisease remains the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Recent studies in young children with CF diagnosed by newborn screening identified neutrophil elastase (NE), a major product released from neutrophils in inflamed airways, as a key risk factor for the onset and early progression of CF lungdisease. However, the understanding of how NE and potentially other proteases contribute to the complex in vivo pathogenesis of CF lungdisease remains limited. In this review, we summarize recent progress in this area based on studies in βENaC-overexpressing (βENaC-Tg) mice featuring CF-like lungdisease and novel protease-specific Förster resonance energy transfer (FRET) sensors for localization and quantification of protease activity in the lung. These studies demonstrated that NE is implicated in several key features of CF lungdisease such as neutrophilic airway inflammation, mucus hypersecretion, and structural lung damage in vivo. Furthermore, these studies identified macrophage elastase (matrix metalloproteinase 12 (MMP12)) as an additional protease contributing to early lung damage in βENaC-Tg mice. Collectively, these results suggest that NE and MMP12 released from activated neutrophils and macrophages in mucus-obstructed airways play important pathogenetic roles and may serve as potential therapeutic targets to prevent and/or delay irreversible structural lung damage in patients with CF. PMID:27456476

To describe the range and frequency of abnormalities on computed tomographic (CT) scans in patients who met the American Thoracic Society (ATS) case definition of Mycobacterium avium complex (MAC) lungdisease. Further, to report the effect of time and treatment on the progression of these abnormalities. The demographic, clinical and radiologic features of 10 patients with proven MAC lungdisease (mean age 71 years, standard deviation 12 years) were described. The presence or absence of 14 CT abnormalities was recorded in each of 10 lung zones. The effects of time and treatment on the abnormalities were recorded. The patients' lung function was minimally impaired. Pretreatment CT scans showed small nodules in 47% of the lung zones, reduced lung attenuation in 41%, and bronchiectasis in 27%. Bronchiectasis was associated with nodules in 20 zones from 9 patients and with no nodules in 7 zones from 1 patient. Reduced attenuation was associated with bronchiectasis alone in 8 zones, with nodules alone in 25 zones and with both bronchiectasis and nodules in 8 zones. In patients without treatment, or with non-curative treatment, bronchiectasis developed or worsened in 12 of 26 zones and resolved or improved in none. In contrast, after curative treatment, small nodules disappeared completely in 10 of 21 zones and developed in none. Of 7 zones with only nodules and reduced attenuation before treatment, 6 had no abnormalities after treatment. Our data suggest that the 3 leading CT abnormalities in nodular-bronchiectatic MAC lungdisease are small nodules, reduced attenuation and bronchiectasis. Reduced attenuation appeared to result from gas trapping and hypoxic vasoconstriction due to bronchiolocentric inflammatory nodules. Bronchiectasis appeared to be secondary to this bronchiolar disease. (author)

To describe the range and frequency of abnormalities on computed tomographic (CT) scans in patients who met the American Thoracic Society (ATS) case definition of Mycobacterium avium complex (MAC) lungdisease. Further, to report the effect of time and treatment on the progression of these abnormalities. The demographic, clinical and radiologic features of 10 patients with proven MAC lungdisease (mean age 71 years, standard deviation 12 years) were described. The presence or absence of 14 CT abnormalities was recorded in each of 10 lung zones. The effects of time and treatment on the abnormalities were recorded. The patients' lung function was minimally impaired. Pretreatment CT scans showed small nodules in 47% of the lung zones, reduced lung attenuation in 41%, and bronchiectasis in 27%. Bronchiectasis was associated with nodules in 20 zones from 9 patients and with no nodules in 7 zones from 1 patient. Reduced attenuation was associated with bronchiectasis alone in 8 zones, with nodules alone in 25 zones and with both bronchiectasis and nodules in 8 zones. In patients without treatment, or with non-curative treatment, bronchiectasis developed or worsened in 12 of 26 zones and resolved or improved in none. In contrast, after curative treatment, small nodules disappeared completely in 10 of 21 zones and developed in none. Of 7 zones with only nodules and reduced attenuation before treatment, 6 had no abnormalities after treatment. Our data suggest that the 3 leading CT abnormalities in nodular-bronchiectatic MAC lungdisease are small nodules, reduced attenuation and bronchiectasis. Reduced attenuation appeared to result from gas trapping and hypoxic vasoconstriction due to bronchiolocentric inflammatory nodules. Bronchiectasis appeared to be secondary to this bronchiolar disease. (author)

Full Text Available Abstract Undifferentiated connective tissue diseases (UCTDs are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported. We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lungdisease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.

Full Text Available Progressive airflow obstruction is a classical hallmark of chronic lungdisease, affecting more than one fourth of the adult population. As the disease progresses, the inner layer of the airway wall grows, folds inwards, and narrows the lumen. The critical failure conditions for airway folding have been studied intensely for idealized circular cross-sections. However, the role of airway branching during this process is unknown. Here, we show that the geometry of the bronchial tree plays a crucial role in chronic airway obstruction and that critical failure conditions vary significantly along a branching airway segment. We perform systematic parametric studies for varying airway cross-sections using a computational model for mucosal thickening based on the theory of finite growth. Our simulations indicate that smaller airways are at a higher risk of narrowing than larger airways and that regions away from a branch narrow more drastically than regions close to a branch. These results agree with clinical observations and could help explain the underlying mechanisms of progressive airway obstruction. Understanding growth-induced instabilities in constrained geometries has immediate biomedical applications beyond asthma and chronic bronchitis in the diagnostics and treatment of chronic gastritis, obstructive sleep apnea and breast cancer.

Rationale: Most children with cystic fibrosis (CF) experience a slow decline in spirometry, although some children continue to be at risk for more significant lungdisease progression. Chest computed tomography (CT) scans have been shown to be more sensitive to changes in lungdisease than spirometry and may provide a means for predicting future lungdisease progression.

Tuberculosis is known to cause both cystic lungdisease and bronchocentric granulomatosis (BCG). However, both are rare manifestations of this common disease. We report a case of BCG with extensive cystic lungdisease in a young female who presented with fever, weight loss, and recurrent pneumothoraces with respiratory failure. Early diagnosis and treatment are imperative, as appropriate therapy may be life-saving in such cases.

Patients with chronic lungdiseases suffer higher symptom burden, lower quality of life, and greater social isolation compared with patients with other diagnoses, such as cancer. These conditions may be alleviated by palliative care, yet palliative care is used less by patients with chronic lungdisease compared with patients with cancer. Underuse is due, in part, to poor implementation of primary palliative care and inadequate referral to specialty palliative care. Lack of primary and specialty palliative care in patients with chronic lungdisease falls short of the minimum standard of competent health care, and represents a disparity in health care and a social injustice. We invoke the ethical principles of justice and sufficiency to highlight the importance of this issue. We identify five barriers to implementing palliative care in patients with chronic lungdisease: uncertainty in prognosis; lack of provider skill to engage in discussions about palliative care; fear of using opioids among patients with chronic lungdisease; fear of diminishing hope; and perceived and implicit bias against patients with smoking-related lungdiseases. We propose mechanisms for improving implementation of palliative care for patients with chronic lungdisease with the goal of enhancing justice in health care. PMID:26730490

Full Text Available Gastro-oesophageal reflux disease (GERD is a common disorder in Western countries, and its relationship to airways disorders (e.g. asthma has been well established. Lungdiseases other than asthma have also been associated with GERD, but the nature and scope of this relationship has not been fully defined. Diseases that have been associated with GERD include bronchiolitis syndromes, idiopathic pulmonary fibrosis, scleroderma and nontubercular mycobacterial infection. Diagnostic evaluation centres upon proving both reflux and pulmonary aspiration, which may be accomplished in some cases by lung biopsy. However, in many cases a compatible clinical and radiographic picture coupled with proof of proximal reflux by combined oesophageal probe testing may suffice for a provisional diagnosis and allow institution of anti-reflux measures. Proton-pump inhibitors are the medications of choice for GERD; other interventions shown to reduce reflux are weight loss, elevation of the head of the bed and avoidance of recumbency after meals. However, acid suppression therapy does not address non-acid reflux that may be important in disease pathogenesis in select patients, and lifestyle modifications often fail. Laparoscopic fundoplication is the procedure of choice for medically refractory GERD with excellent short-term results with respect to respiratory symptoms associated with GERD; however, long-term studies document a significant percentage of patients requiring ongoing acid suppression therapy.

Full Text Available Thad E Abrams,1,2 Amy Blevins,1,3 Mark W Vander Weg1,2,4 1Department of Internal Medicine, University of Iowa, 2Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, 3Hardin Health Sciences Library, 4Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Background: Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature.Objectives: The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1 determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2 identify targeted areas for further research.Methods: A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1 the co-occurrence of COPD and PTSD and 2 the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology.Results: A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD

Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lungdisease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker. PMID:26410982

Background The relationship between inflammation, air obstruction and lung cancer is complex and there is still great uncertainty regarding their underlying pathophysiology. Our aim was to investigate the inflammation pathways that are implicated in both chronic obstructive pulmonary disease (COPD) and lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The pathophysiology of both COPD and lung cancer includes dysreg...

70 lungs scans using gallium 67 were carried out. Among the 41 malignant lesions, an uptake of the radio-isotope by the tumour in 51% of cases was noted. Among the 29 benign lesions, there were also 34% of cases which took up gallium 67. Their lack of reliability and selectivity make gallium 67 lung scans unsuitable for the recognition of the malignant nature of lungdiseases

Coronary artery disease (CAD) is not uncommon among lung transplant candidates. Several small, single-center series have suggested that short-term outcomes are acceptable in selected patients who undergo coronary revascularization prior to, or concomitant with, lung transplantation. Our objective was to evaluate perioperative and intermediate-term outcomes in this patient population at our institution. We performed a retrospective, observational cohort analysis of 898 lung transplant recipien...

PURPOSE OF REVIEW:Chronic obstructive pulmonary disease (COPD) and lung cancer are the leading causes of morbidity and mortality worldwide. The current research is focused on identifying the common and disparate events involved in epigenetic modifications that concurrently occur during the pathogenesis of COPD and lung cancer. The purpose of this review is to describe the current knowledge and understanding of epigenetic modifications in pathogenesis of COPD and lung cancer.RECENT FINDINGS:Th...

Lungdisease and lung injury are responsible for 20% of deaths of the Irish population every year, and the country has the 2nd highest death rate in Europe for respiratory diseases. Conditions related to the respiratory system are the second largest long term illness by young adults. Lung cancer is the largest cause of cancer related death in Europe as a whole. New and refined mechanisms of drug delivery for the prevention, cure or delayed progression of disease, represents a pathway for t...

BACKGROUND: For lung cancer patients with poor pulmonary function due to emphysema or fibrosis, it is important to predict the amplitude of internal tumor motion to minimize the irradiation of the functioning lung tissue before receiving stereotactic body radiotherapy. MATERIALS AND METHODS: Two board-certified diagnostic radiologists independently assessed the degree of pulmonary emphysema and fibrosis on computed tomography (CT) in 71 patients with peripheral lung tumors before real-time tu...

Chronic obstructive pulmonary disease (COPD) is a devastating disease.While there is no cure for COPD and the lung damage associated with this disease cannot be reversed, it is still very important to diagnose it as early as possible. In this paper, we propose a novel method based on the measurement of air trapping in the lungs from CT images to detect COPD and to evaluate its severity. Twenty-five patients and twelve normal adults were included in this study. The proposed method found volumetric changes of the lungs from inspiration to expiration. To this end, trachea CT images at full inspiration and expiration were compared and changes in the areas and volumes of the lungs between inspiration and expiration were used to define quantitative measures (features). Using these features,the subjects were classified into two groups of normal and COPD patients using a Bayesian classifier. In addition, t-tests were applied to evaluate discrimination powers of the features for this classification. For the cases studied, the proposed method estimated air trapping in the lungs from CT images without human intervention. Based on the results, a mathematical model was developed to relate variations of lung volumes to the severity of the disease. As a computer aided diagnosis (CAD) system, the proposed method may assist radiologists in the detection of COPD. It quantifies air trapping in the lungs and thus may assist them with the scoring of the disease by quantifying the severity of the disease

Abstract Effects of pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and lung tuberculosis (TB)] on subsequent lung cancer development have been reported. However, whether patients with coexisting pulmonary diseases are at greater risk of developing various histologic types of lung cancer remains elusive. Patients newly diagnosed with lung cancer between 2004 and 2008 were identified from National Health Insurance Research Database (Taiwan). The histologic types of lu...

Full Text Available Aim: Interstitial lungdiseases are a heterogeneous group of diseases with a known or unknown etiology affecting the interstitium of the lung. In this study, our experience in the lung biopsy performed by video-assisted thoracoscopic surgery and open lung biopsy for interstitial lungdiseases is discussed. Material and Method: In this study, we reviewed 31 patients with a clinical diagnosis of interstitial lungdisease who underwent open or thoracoscopic lung biopsy between the years of 2004 and 2010. The cases were examined retrospectively for the age, sex, radiological appearance, operative time, chest tube duration, postoperative hospital stay and the complications. Thoracotomy was performed to 19 of the patients (61.30% while twelve patients (38.70% underwent video-assisted thoracoscopic surgery. Result: Fourteen of the cases (45.16% were male while 17 patients were female (58.06% with a mean age of 40.83 15.537 (18-69. Nonspecific interstitial fibrosis constituted the most of the certain diagnoses (29.27%. Operative time, chest tube duration and postoperative hospital stay were significantly shorter in video-assisted thoracoscopic surgery group (p values were 0.018, 0.001 and 0.011 respectively. The overall morbidity rate was 12.90% and there was no mortality. Discussion: In spite of recent advances in clinical diagnostic techniques, lung biopsy is the gold standard for the diagnosis of interstitial lungdisease. In our opinion, video-assisted thoracoscopic surgery should be the first choice in the diagnosis of interstitial lungdiseases, since these patients can be discharged early as a result of shorter chest tube duration and hospital length of stay

The chronic fibrosing idiopathic interstitial pneumonias (IIPs) are a group of heterogeneous pulmonary parenchymal disorders described by radiologic and histological patterns termed usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). These include idiopathic pulmonary fibrosis (IPF) and those related to connective tissue disease (CTD) and are associated with substantial morbidity and mortality. Beyond the importance of establishing an appropriate diagnosis, designing optimal clinical trials for IIPs has been fraught with difficulties in consistency of clinical endpoints making power analyses, and the establishment of efficacy and interpretation of results across trials challenging. Preliminary recommendations, developed by rigorous consensus methods, proposed a minimum set of outcome measures, a ‘core set’, to be incorporated into future clinical trials (Saketkoo et al, THORAX. 2014.). This paper sets out to examine the candidate instruments for each domain (Dyspnea, Cough, Health Related Quality of Life, Imaging, Lung Physiology and Function, Mortality). Candidate measures that were not selected as well as measures that were not available for examination at the time of the consensus process will also be discussed. PMID:27019654

Method of diagnosis of chronic nonspecific diseases of lungs in children using bronchography and arteriography is suggested to improve diagnosis accuracy. The method lies in simultaneous contrasting of all bronchial arteries of both lungs. The suggested method of diagnosis enabled to obtain data on pathology of bronchial arteries and bronchial structurs, to reveal additional information about propogation and character of pathologic process

Whether nontuberculous mycobacterial (NTM) disease is a contraindication to lung transplantation remains controversial. We conducted a nationwide study to evaluate the clinical importance of NTM infection among lung transplant patients with cystic fibrosis (CF) in Denmark and to determine if NTM...

Rationale Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty in obtaining lung tissue samples from individuals with impaired lung function. Objectives: We sought to determine whether COPD-associated processes are reflected in gene express

Nonuniform distribution (NUD) of perfusion on single photon emission computed tomography (SPECT) is caused by impaired perfusion-related fluctuations of the functional volume (FFV). It was determined if digital analysis of NUD in each hemi-lung damaged by chronic obstructive pulmonary disease (COPD) could improve the whole lung impairment assessment. We examined 665 subjects and 8 controls by SPECT. The basic whole lung SPECT volume was defined at 10% of maximum whole lung count cutoff threshold (T h). For the whole lung and each hemi-lung, the 10% T h width volume, FFV rate, and misfit from the control were calculated at every T h width number (n) from 1 to 9 for every additional 10% T h from 10 to 100%. The misfit value integrated from 1 to 9 of n was defined by 3 NUD indices: D, whole lung NUD index; D rl , the index for the sum of each hemi-lung NUD; and D (I) , the NUD index with every interpolating pattern in which FFV rates of hemi-lungs comprised negative and positive value at the same n. D rl index was the sum of D and D (I) indices in all patients. D rl and D indices significantly increased in pulmonary disease subjects relative to those of the normal group and non-pulmonary disease subjects. D rl and D indices increased in COPD subjects. Progressive COPD subjects had larger D rl index values and "diffuse and even" hemi-lung impairment. The three indices quantizing FFV itself leading to NUD helped to digitally evaluate the degree of lung impairment of perfusion. Clinically, it is expected that the NUD indices and images obtained by SPECT, which visually and digitally show the pathological fluctuations in perfusion caused by lung impairment, will be able to provide specific and useful information for improving treatment and/or care of subjects with COPD. PMID:26644008

Full Text Available Yeon Wook Kim,1 Kwang-Nam Jin,2 Eun Young Heo,3 Sung Soo Park,3 Hee Soon Chung,3 Deog Kyeom Kim31Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of KoreaBackground: Whereas the epidemiological association between lung cancer and chronic obstructive pulmonary disease (COPD, a chronic inflammatory respiratory disease, is well known, limited studies have examined the association between lung cancer and non-cystic fibrosis bronchiectasis, a representative chronic airway inflammatory disease. This study evaluated the association between bronchiectasis and lung cancer in patients with COPD.Methods: A matched case–control study was conducted in a referral hospital in South Korea. Among COPD patients with moderate to very severe airflow limitation (forced expiratory volume in one second/forced vital capacity <0.7 and forced expiratory volume in one second ≤70% [% predicted] who underwent chest computed tomography (CT between January 1, 2010 and May 30, 2013, patients with lung cancer and controls matched for age, sex, and smoking history were selected. The risk of lung cancer was assessed according to the presence of underlying bronchiectasis confirmed by chest CT.Results: The study enrolled 99 cases and 198 controls. Combined bronchiectasis on chest CT was inversely associated with the risk of lung cancer compared with controls (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.12–0.52, P<0.001. Significant associations were found in

Occupational and environmental lungdiseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lungdiseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lungdisease is an occupational interstitial lungdisease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lungdiseases. PMID:24388365

Pulmonary involvement during systemic sclerosis (SS) is dominated by interstitial lungdisease and arterial pulmonary hypertension. It is about a retrospective study analyzing 65 cases of SS over a period of 13 years. We compared cases with and without interstitial lungdisease. The diagnosis of SS was retained according to American College of Rheumatology (ACR)/EULAR 2013 criteria. The diagnosis of interstitial lungdisease was retained in TDM and EFR. Pulmonary hypertension is defined by a pulmonary arterial pression higher than 25 mmHg. The mean delay of diagnosis of interstitial lungdisease and the diagnosis was of 48 months (extremes 0-78 months). The comparison between both groups according to average age of the patients, prevalence of pulmonary hypertension, frequency of Raynaud phenomenon and trophic disorders did not find any significant difference. Lung involvement was associated with an esophageal involvement in 71% of the cases (P=0.059). Antibodies anti-Scl 70 were noted more frequently in patient's with interstitial lungdisease (79% of the cases, P=0.001). Patients were treated with colchicine and vitamin E. A corticotherapy had been indicated at a single patient. The evolution of SS was marked by the stabilisation of the restrictive syndrome in 71.8% of the cases and a worsening in 25% of the cases. Early and appropriate diagnosis of SS and screening of lung involvement are essential for a early care. PMID:26651932

Dendritic cells (DCs) significantly contribute to the pathology of several mouse lungdisease models. However, little is known of the contribution of DCs to human lungdiseases. In this study, we examined infiltration with BDCA1+ DCs of human lungs in patients with interstitial lungdiseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1+ DCs, we found that the numbers of BDCA1+ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1+ DCs in human lungdiseases associated with interstitial fibrosis or Th2 airway inflammation. PMID:24915147

Lung studies by nuclear techniques have been mostly neglected so far in the developing countries because ''total lung imaging'' was not possible. The availability of radioaerosols had now provided means to do complete lung studies in these countries. IAEA's effort to make radioaerosol techniques more widely available in the Asian countries has been most noteworthy. Pulmonary tuberculosis is still prevalent in the developing countries, scourge of smoking is becoming increasingly wide spread and atmospheric pollution is on the rise as these countries race towards industrialisation with insufficient technical and financial resources. These conditions would provide a fascinating backdrop of infective, cancerous and pollution-induced conditions of lungs where lung imaging techniques would have a large scope of providing useful service

Purpose: For lung cancer patients with poor pulmonary function because of emphysema or fibrosis, it is important to predict the amplitude of internal tumor motion to minimize the irradiation of the functioning lung tissue before undergoing stereotactic body radiotherapy. Methods and Materials: Two board-certified diagnostic radiologists independently assessed the degree of pulmonary emphysema and fibrosis on computed tomography scans in 71 patients with peripheral lung tumors before real-time tumor-tracking radiotherapy. The relationships between the computed tomography findings of the lung parenchyma and the motion of the fiducial marker near the lung tumor were investigated. Of the 71 patients, 30 had normal pulmonary function, and 29 had obstructive pulmonary dysfunction (forced expiratory volume in 1 s/forced vital capacity ratio of <70%), 6 patients had constrictive dysfunction (percentage of vital capacity <80%), and 16 had mixed dysfunction. Results: The upper region was associated with smaller tumor motion, as expected (p = .0004), and the presence of fibrosis (p = .088) and pleural tumor contact (p = .086) were weakly associated with tumor motion. The presence of fibrotic changes in the lung tissue was associated with smaller tumor motion in the upper region (p lung region with fibrotic changes have smaller motion than those in the upper region of the lungs without fibrotic changes. The tumor motion in the lower lung region was not significantly different between patients with and without lung fibrosis. Emphysema was not associated with the amplitude of tumor motion.

Outbreaks of infections by rapidly growing mycobacteria following invasive procedures, such as ophthalmological, laparoscopic, arthroscopic, plastic, and cardiac surgeries, mesotherapy, and vaccination, have been detected in Brazil since 1998. Members of the Mycobacterium chelonae-Mycobacterium abscessus group have caused most of these outbreaks. As part of an epidemiological investigation, the isolates were typed by pulsed-field gel electrophoresis (PFGE). In this project, we performed a lar...

Anti-interferon (IFN)-γ autoantibodies are increasingly recognized as a cause of adult-onset immunodeficiency and increased risk for infections with intracellular pathogens. We report on disseminated Talaromyces (Penicillium) marneffei and Mycobacterium abscessus infection in a 72-year-old, human immunodeficiency virus noninfected, Thai man with anti-IFN-γ autoantibody. The patient was successfully treated with antimicrobial therapy and rituximab to control B cell-derived autoantibodies. PMID:27419165

Abstract Background Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended ...

Full Text Available Abstract Background Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended this Oriental medicine clinic. Methods Patients were defined as clinic patients with persistent cutaneous infections at the acupuncture sites. Medical records for the previous 7 months were reviewed. Clinical specimens were obtained from the patients and an environmental investigation was performed. M. abscessus isolates, cultured from patients, were compared by pulsed-field gel electrophoresis (PFGE. Results Forty patients who attended the Oriental medicine clinic and experienced persistent cutaneous wound infections were identified. Cultures from five of these patients proved positive, and all other diagnoses were based on clinical and histopathologic examinations. All environmental objects tested were negative for M. abscessus, however, most were contaminated by various nosocomial pathogens. Molecular analysis using PFGE found all wound isolates to be identical. Conclusion We have identified a large outbreak of rapidly growing mycobacterial infection among patients who received acupuncture at a single Oriental medicine clinic. Physicians should suspect mycobacterial infections in patients with persistent cutaneous infections following acupuncture, and infection control education including hygienic practice, should be emphasized for Oriental medical doctors practicing acupuncture.

Background: There are very few studies are done on spirometry and X-ray findings in interstitial lungdiseases (ILD) in India. Methods: Pulmonary function tests were performed on computerized spirometer, through Kit Microsystems in 30 patients of high resolution computed tomography (HRCT) proven interstitial lungdiseases in tertiary care centre. Results: Majority were in age group 40-49 years (mean age-45.23 years) and 66.5% male patients. Restrictive pattern (96.57%) was present in majority...

As a coordinated research project of the International Atomic Energy Agency (IAEA), a multicentre joint study on radioaerosol lung scan using the BARC nebulizer has prospectively been carried out during 1988-1992 with the participation of 10 member countries in Asia [Bangladesh, China, India, Indonesia, Japan, Korea, Pakistan, Philippines, Singapore and Thailand]. The study was designed so that it would primarily cover chronic obstructive pulmonary disease (COPD) and the other related and common pulmonary diseases. The study also included normal controls and asymptomatic smokers. The purposes of this presentation are three fold: firstly, to document the usefulness of the nebulizer and the validity of user's protocol in imaging COPD and other lungdiseases; secondly, to discuss scan features of the individual COPD and other disorders studied and thirdly, to correlate scan alterations with radiographic findings. Before proceeding with a systematic analysis of aerosol scan patterns in the disease groups, we documented normal pattern. The next step was the assessment of scan features in those who had been smoking for more than several years but had no symptoms or signs referable to airways. The lungdiseases we analyzed included COPD [emphysema, chronic bronchitis, asthma and bronchiectasis], bronchial obstruction, compensatory overinflation and other common lungdiseases such as lobar pneumonia, tuberculosis, interstitial fibrosis, diffuse panbronchiolitis, lung edema and primary and metastatic lung cancers. Lung embolism, inhalation bums and glue-sniffer's lung are separately discussed by Dr. Sundram of Singapore elsewhere in this book. The larger portion of this chapter is allocated to the discussion of COPD with a special effort made in sorting out differential scan features. Diagnostic criteria in individual COPD were defined for each category of disease and basic clinical symptoms and signs and pertinent laboratory data as well as radiographic manifestations are

Lungdisease is the major cause of death and hospitalization worldwide. Transcription factors such as transcription factor 7 (TCF7) are involved in the pathogenesis of lungdiseases. TCF7 is important for T cell development and differentiation, embryonic development, or tumorogenesis. Multiple TCF7 isoforms can be characterized by the full-length isoform (FL-TCF7) as a transcription activator, or dominant negative isoform (dn-TCF7) as a transcription repressor. TCF7 interacts with multiple pr...

The term diffuse interstitial lungdisease, it refers to those diseases that commit the interstice basically, the space between the membrane basal epithelial and endothelial, although the damage can also commit the outlying air spaces and the vessels; the supplement is centered in the diffuse interstitial lung illness of unknown cause; well-known as idiopathic interstitial pneumonias, making emphasis in the more frequents, the pulmonary fibrosis idiopathic or cryptogenic fibrosant alveolitis

Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970. The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population. The pertinent clinical data from these patients are described and compared to 28 additional patients reported from other institutions. Small-cell lung cancer represented the predominant histologic type of lung cancer encountered in both smoking and nonsmoking patients with HD, accounting for 42% of cases overall and greater than 55% of cases reported in reviews of second malignancies. Tobacco use was noted in only 53% of patients. Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD. Nineteen (68%) of these patients received subsequent chemotherapy salvage. The median age at diagnosis of HD and lung cancer was 39 and 45 years, respectively. The interval between diagnosis of HD and metachronous lung cancer averaged seven years but appeared to vary inversely with age. HD patients treated with supradiaphragmatic irradiation or combined modality therapy may be at increased risk for developing lung cancer. The high frequency of in-field malignancies that the authors observed and the prevalence of small-cell lung cancer in both smoking and nonsmoking patients suggests that chest irradiation may influence the development of metachronous lung cancer in these patients. The finding of a mean latent interval in excess of seven years emphasizes the need for close long-term observation.

The purpose of the study was to quantify the unevenness of perfusion distribution in the lungs in conjunction with underlying lung pathology. Twenty-one parameters as described previously were defined out of horizontal radioactive count profiles on perfusion lung image data taken in 64x64 matrixes. Principal component analysis has revealed that the 1st component or Z1 is represented by AREA, the area of the lung, and ANG, the slope of the mean count profile, Z2, by N, the number of peaks, Z3 and Z4, by YG and XG, the barycentric coordinates of count distribution, Z5, by MAC, the maximal count and Z6, by CSD, the degree of scatter in count from the peak count. How those parameters differ in each lung pathology has been determined from 657 lung perfusion image data. In pulmonary emphysema, the lung volumes are larger than those in normal subjects. The AREA and ANG were consequently larger in value and N was also significantly larger, indicating the increased regional alveolar pressure and the compressed or destroyed vascular beds. In diffuse panbronchiolitis (DPB), N was increased probably because the distal airways were either narrowed or obstructed by inflammatory processes inducing regional alveolar hypoxia and/or alveolar hyperinflation. In fibrosis, both AREA and N were significantly smaller. In congestive heart failure with postcapillary pulmonary hypertension, YG was smaller probably because of 'reversal of perfusion'. In pulmonary sarcoidosis, an increase in YG was the only abnormality. (author)

The purpose of the study was to quantify the unevenness of perfusion distribution in the lungs in conjunction with underlying lung pathology. Twenty-one parameters as described previously were defined out of horizontal radioactive count profiles on perfusion lung image data taken in 64x64 matrixes. Principal component analysis has revealed that the 1st component or Z1 is represented by AREA, the area of the lung, and ANG, the slope of the mean count profile, Z2, by N, the number of peaks, Z3 and Z4, by YG and XG, the barycentric coordinates of count distribution, Z5, by MAC, the maximal count and Z6, by CSD, the degree of scatter in count from the peak count. How those parameters differ in each lung pathology has been determined from 657 lung perfusion image data. In pulmonary emphysema, the lung volumes are larger than those in normal subjects. The AREA and ANG were consequently larger in value and N was also significantly larger, indicating the increased regional alveolar pressure and the compressed or destroyed vascular beds. In diffuse panbronchiolitis (DPB), N was increased probably because the distal airways were either narrowed or obstructed by inflammatory processes inducing regional alveolar hypoxia and/or alveolar hyperinflation. In fibrosis, both AREA and N were significantly smaller. In congestive heart failure with postcapillary pulmonary hypertension, YG was smaller probably because of 'reversal of perfusion'. In pulmonary sarcoidosis, an increase in YG was the only abnormality. (author).

Highlights: •The distribution of cystic lesions in LAM was evaluated with quantitative CT. •There were more cystic lesions in the central lung compared to peripheral areas. •Cystic changes were more frequent in apical two thirds compared to lower third. •Results might help to obviate the need for biopsy in more cases. -- Abstract: Purpose: Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). Materials and methods: CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a “peel” and “core” of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density lung. Results: Cystic changes accounted for 0.1–39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p = 0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower

Highlights: •The distribution of cystic lesions in LAM was evaluated with quantitative CT. •There were more cystic lesions in the central lung compared to peripheral areas. •Cystic changes were more frequent in apical two thirds compared to lower third. •Results might help to obviate the need for biopsy in more cases. -- Abstract: Purpose: Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). Materials and methods: CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a “peel” and “core” of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density lung. Results: Cystic changes accounted for 0.1–39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p = 0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower

Objective This review focuses on current knowledge of specific processes that drive chronic airway inflammation which are important in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and lung cancer.Data sources The data used in this review were obtained mainly from studies reported in the PubMed database (1997-2012) using the terms of COPD and lung cancer.Study selection Data from published articles about prevalence of COPD-lung cancer overlap and mechanism involved in lung cancer development in COPD were identified,retrieved and reviewed.Results COPD prevalence,morbidity and mortality vary and are directly related to the prevalence of tobacco smoking except in developing countries where air pollution resulting from the burning of biomass fuels is also important.COPD is characterized by a chronic inflammation of lower airway and,importantly,the presence of COPD increases the risk of lung cancer up to 4.5 fold among long-term smokers.COPD is by far the greatest risk factor for lung cancer amongst smokers and is found in 50％-90％ of patients with lung cancer.Conclusions Both COPD and lung cancer are tobacco smoking-associated chronic diseases that cluster in families and aggravate with age,and 50％-70％ of patients diagnosed with lung cancer have declined spirometric evidence of COPD.Understanding and targeting common pathogenic mechanisms for lung cancer and COPD would have potential diagnostic and therapeutic implications for patients with these lungdiseases and for people at risk.

Full Text Available Abstract Restrictive lungdisease is a broad term encompassing a number of conditions in which lung volumes are reduced. Dyspnea is a common clinical manifestation of restrictive lungdisease and frequently becomes a prominent and disabling symptom that undermines patients' ability to function and engage in activities of daily living (especially in those with more advanced restriction. Effective management of this disabling symptom awaits a better understanding of its underlying physiology. In recent decades, our understanding of the mechanisms of dyspnea in restrictive lungdisease has been improved by a small, but significant, body of research. One approach to the study of dyspnea is to identify the major qualitative dimensions of the symptom in an attempt to uncover different underlying neurophysiologic mechanisms. This article will review the existing literature on the intensity and qualitative dimensions of dyspnea during exercise in patients with restrictive lungdisease. The main focus will be on interstitial lungdisease (ILD, since it is the prototypical restrictive disease.

There is increased awareness of smoking-related lungdiseases other than lung cancer and chronic obstructive pulmonary disease. Concurrently, there is general acceptance that there is difficulty in establishing a specific diagnosis of smoking-related interstitial lungdisease (ILD), as many patients may not undergo biopsy to facilitate a specific histopathologic diagnosis. Cases that do proceed to biopsy may demonstrate multiple abnormalities, and histologic overlap between different disease processes may confound the picture. This review outlines the key aspects of smoking-related lungdisease, including entities secondary to smoking-related lung inflammation such as respiratory bronchiolitis-ILD, desquamative idiopathic pneumonia, and pulmonary Langerhans cell histiocytosis, as well as chronic fibrosing lungdiseases strongly associated with cigarette smoke including idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, nonspecific interstitial pneumonia, and rheumatoid arthritis-ILD. The focus will be on incorporation of clinical findings, key pulmonary function testing parameters, high-resolution computer tomography (HRCT) findings, and pathologic correlates in refining the differential diagnosis and differentiating between the various entities. PMID:26479130

The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lungdiseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lungdiseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and the prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model. (au)

Highly purified type-specific anti-collagen antibodies (prepared in animals to types I, II, III, and IV bovine collagen) were used in an indirect immunofluorescence method for the study of human lung collagen. The tissue localisation of each collagen type, and the apparent type I:III collagen ratio was assessed in normal foetal and adult lung and in fibrotic lung lesions. In the latter, the relationship of the findings to the natural history of the lesion was considered. This method was compa...

Full Text Available Abstract Background In neonatology the role of chest physiotherapy is still uncertain because of the controversial outcomes. Methods The aim of this study was to test the applicability in preterm infants of 'reflex rolling', from the Vojta method, in preterm neonates with lung pathology, with particular attention to the effects on blood gases and oxygen saturation, on the spontaneous breathing, on the onset of stress or pain. The study included 34 preterm newborns with mean gestational age of 30.5 (1.6 weeks - mean (DS - and birth weight of 1430 (423 g - mean (DS -, who suffered from hyaline membrane disease, under treatment with nasal CPAP (continuous positive airways pressure, or from pneumonia, under treatment with oxygen-therapy. The neonates underwent phase 1 of 'reflex rolling' according to Vojta method three times daily. Respiratory rate, SatO2, transcutaneous PtcCO2 e PtcO2 were monitored; in order to evaluate the onset of stress or pain following the stimulations, the NIPS score and the PIPP score were recorded; cerebral ultrasound scans were performed on postnatal days 1-3-5-7, and then weekly. Results In this population the first phase of Vojta's 'reflex rolling' caused an increase of PtcO2 and SatO2 values. No negative effects on PtcCO2 and respiratory rate were observed, NIPS and PIPP stress scores remained unmodified during the treatment; in no patient the intraventricular haemorrhage worsened in time and none of the infants developed periventricular leucomalacia. Conclusions Our experience, using the Vojta method, allows to affirm that this method is safe for preterm neonates, but further investigations are necessary to confirm its positive effects and to evaluate long-term respiratory outcomes.

Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lungdisease. People who smoke are more seriously affected and have a greater risk of dying from the disease.......Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lungdisease. People who smoke are more seriously affected and have a greater risk of dying from the disease....

Human lung growth and development begins with preconception exposures and continues through conception and childhood into early adulthood. Numerous environmental exposures (both positive and negative) can affect lung health and disease throughout life. Infant lung health correlates with adult lung function, but significant knowledge gaps exist regarding the influence of preconception, perinatal, and postnatal exposures on general lung health throughout life. On October 1 and 2, 2015, the National Heart, Lung, and Blood Institute convened a group of extramural investigators to develop their recommendations for the direction(s) for future research in prenatal and perinatal determinants of lung health and disease in early life and to identify opportunities for scientific advancement. They identified that future investigations will need not only to examine abnormal lung development, but also to use developing technology and resources to better define normal and/or enhanced lung health. Birth cohort studies offer key opportunities to capture the important influence of preconception and obstetric risk factors on lung health, development, and disease. These studies should include well-characterized obstetrical data and comprehensive plans for prospective follow-up. The importance of continued basic science, translational, and animal studies for providing mechanisms to explain causality using new methods cannot be overemphasized. Multidisciplinary approaches involving obstetricians, neonatologists, pediatric and adult pulmonologists, and basic scientists should be encouraged to design and conduct comprehensive and impactful research on the early stages of normal and abnormal human lung growth that influence adult outcome. PMID:26953657

Recurrent bacterial infections in Cystic Fibrosis (CF) are the primary cause for morbidity and mortality in CF. Advancements in second generation sequencing and evolution of the lung microbiome has prompted greater interest in other bacteria present in the lung. Anaerobic bacteria have been one of the most common bacteria found on molecular sequencing, their cause and role is as of yet unknown. In our project, we recruited 450 patients prospectively and followed them at both stable and exacer...

Chronic lungdiseases are common causes of pulmonary hypertension. It ranks second after the left heart disease. Both obstructive and restrictive lungdiseases are know to cause pulmonary hypertension. The pathophysiology of the disease is complex, and includes factors affecting the blood vessels, airways, and lung parenchyma. Hypoxia and the inhalation of toxic materials are another contributing factors. Recent guidelines have further clarified the association between pulmonary hypertens...

Lung scintiscanning was performed to investigate the distribution of pulmonary blood flow before and after surgery in 30 patients with tetralogy of Fallot. Uniformity of lung scintigram and the derangement of the distribution pattern were observed preoperatively and postoperatively. The results were as follows: 1) Preoperatively, uniformity of lung scintigram was 27.7 - 100% (average 63.4%). It is more necessary to construct the outflow tract in most cases, when the PA/Ao diameter ratio was lower than 0.5 and uniformity of lung scintigram was under 50%. Besides, preoperative uniformity of lung scintigram correlated with the degree of polycythemia. In 3 cases who died after corrective surgery, the value of uniformity of lung scintigram was as low as 33.3 - 61.1%. 2) Preoperative pulmonary blood flow disturbances were found in 50% of 30 cases. In all of the cases without pulmonary blood flow disturbances, total correction was successfully performed. On the other hand, in cases with pulmonary blood flow disturbances, the result of total correction was not satisfactory. 3) In cases with the slight and moderately deranged distribution preoperatively, postoperative follow up study by scintiscanning at 1 to 2 months after surgery showed considerately more improvement of pulmonary blood flow. (author)

can also rule out airway obstruction in patients with respiratory symptoms caused by other illnesses, such as heart failure or lung cancer. Initiating medication for obstructive lungdisease without spirometry entails the risk of these patients experiencing unnecessary delay in the diagnostic process...... medication targeting obstructive lungdisease within the first year and redeeming medication repeatedly increased the odds of having spirometry performed. Women and patients in the oldest age categories had reduced odds of having spirometry performed. Being unemployed reduced the odds for spirometry testing......-infectious dyspnoea, chronic cough and wheezing are common symptoms in the population. Patients often present with these symptoms in general practice and have a high probability of having obstructive lungdiseases. However, there is an indication that the majority of these patients are treated empirically with...

INTRODUCTION: We hypothesized that statin use begun before the diagnosis of interstitial lungdisease is associated with reduced mortality. METHODS: We studied all patients diagnosed with interstitial lungdisease in the entire Danish population from 1995 through 2009, comparing statin use versus...... no statin use in a nested 1:2 matched study. RESULTS: The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lungdisease (n = 1,786+3,572) and idiopathic lung fibrosis (n = 261+522) was higher for statin users versus never users (log-rank: P = 7·10-9 and P...... statin use was associated with reduced all-cause mortality....

Abstract Background The molecular pathways involved in the interstitial lungdiseases (ILDs) are poorly understood. Systems biology approaches, with global expression data sets, were used to identify perturbed gene networks, to gain some understanding of the underlying mechanisms, and to develop specific hypotheses relevant to these chronic lungdiseases. Methods Lung tissue samples from patients with different types of ILD were obtained from the Lung Tissue Research Consortium and total cell...

Full Text Available Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lungdisease. Recognition of occupational lungdisease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT is superior in delineating the lung architecture and depicting pathology. The characteristic radiological features suggest the correct diagnosis in some, whereas a combination of clinical features, occupational history, and radiological findings is essential in establishing the diagnosis in others. In the presence of a history of exposure and consistent clinical features, the diagnosis of even an uncommon occupational lungdisease can be suggested by the characteristic described HRCT findings. In this article, we briefly review the HRCT appearance of a wide spectrum of occupational lungdiseases.

Full Text Available Abstract Background A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. Methods The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lungdisease, such as Acute Respiratory Distress Syndrome (ARDS. The model was directly connected to a ventilator and the resulting pressure volume curves recorded. Results The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. Conclusion Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lungdiseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp.

After a mathematical extension of the existing model for the theoretical description of the aerosol bolus dispersion, the behavior of particle pulses in diseasedlung structures was simulated. The geometry used for healthy lungs was modified in two aspects: First, a modelling of possible airway obstructions, which usually occur in patients with chronic bronchitis, chronic asthma or cystic fibrosis, was carried out and, second, a theoretical approximation of the emphysema, being observed in lungs of smokers, but also as an accompanying phenomenon in obstructive diseases, was established. According to the modified model, in lungs with airway obstructions the exhaled bolus exhibited a decreased dispersion with respect to healthy subjects, whereas in emphysematous lungs the respective half-width of the peak was increased. Standard deviation and skewness of the bolus were similarly influenced by the modified lung architecture. A combination of airway obstruction and emphysema caused an extensive compensation of individual dispersion effects, complicating a secure distinction from the healthy lung. According to the model, a special diagnostic value may be assigned to the bolus deposition, showing significant deviations from the normal case for all simulated diseases. (orig.)

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lungdisease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lungdisease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lungdiseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lungdisease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lungdiseases. PMID:25644583

Research from the wars in Afghanistan and Iraq have focused on traumatic brain injury (TBI) and mental health conditions; however, it is becoming clear that other health concerns, such as respiratory illnesses, warrant further scientific inquiry. Early reports from theater and postdeployment health assessments suggested an association with deployment-related exposures (e.g., sand, burn pits, chemical, etc.) and new-onset respiratory symptoms. We used data from Veterans Affairs medical encounters between fiscal years 2003 and 2011 to identify trends in chronic obstructive pulmonary disease, asthma, and interstitial lungdisease in veterans. We used data from Veterans Affairs and Department of Defense sources to identify sociodemographic (age, sex, race), military (e.g., service branch, multiple deployments) and clinical characteristics (TBI, smoking) of individuals with and without chronic lungdiseases. Generalized estimating equations found significant increases over time for chronic obstructive pulmonary disease and asthma in both unadjusted and adjusted analyses. Trends for interstitial lungdisease were significant only in adjusted analyses. Age, smoking, and TBI were also significantly associated with chronic lungdiseases; however, multiple deployments were not associated. Research is needed to identify which characteristics of deployment-related exposures are linked with chronic lungdisease. PMID:27136656

Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue in the lungs of patients with idiopathic pulmonary fibrosis. Multiple resident pulmonary cell types and bone marrow-derived fibrocytes have been implicated as contributors to fibrotic lesions because of the transdifferentiation potential of these cells into myofibroblasts. In this study, we assessed the expression of Wilms tumor 1 (WT1), a known marker of mesothelial cells, in various cell types in normal and fibrotic lungs. We demonstrate that WT1 is expressed by both mesothelial and mesenchymal cells in idiopathic pulmonary fibrosis lungs but has limited or no expression in normal human lungs. We also demonstrate that WT1(+) cells accumulate in fibrotic lung lesions, using two different mouse models of pulmonary fibrosis and WT1 promoter-driven fluorescent reporter mice. Reconstitution of bone marrow cells into a TGF-α transgenic mouse model demonstrated that fibrocytes do not transform into WT1(+) mesenchymal cells, but they do augment accumulation of WT1(+) cells in severe fibrotic lungdisease. Importantly, the number of WT1(+) cells in fibrotic lesions was correlated with severity of lungdisease as assessed by changes in lung function, histology, and hydroxyproline levels in mice. Finally, inhibition of WT1 expression was sufficient to attenuate collagen and other extracellular matrix gene production by mesenchymal cells from both murine and human fibrotic lungs. Thus, the results of this study demonstrate a novel association between fibrocyte-driven WT1(+) cell accumulation and severe fibrotic lungdisease. PMID:26371248

The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomography (18F-FDG PET) for the non-invasive differentiation of focal lung lesions originated from cancer or inflammation disease by combined visual image interpretation and semi-quantitative uptake value analysis has been documented. In general, Standardized Uptake Value (SUV) is used to diagnose lungdisease. But SUV dose not contain dynamic information of lung tissue for the glucose. Therefore, this study was undertaken to hypothesis that analysis of dynamic kinetics of focal lung lesions base on 18F-FDG PET may more accurately determine the lungdisease. So we compared Time Activity Curve (TAC), Standardized Uptake Value-Dynamic Curve (SUV-DC) graph pattern with Glucose Metabolic Rate (MRGlu) from Patlak analysis. With lungdisease, 17 patients were examined. They were injected with 18F-FDG over 30-s into peripheral vein while acquisition of the serial transaxial tomographic images were started. For acquisition protocol, we used twelve 10-s, four 30-s, sixteen 60-s, five 300-s and one 900-s frame for 60 mins. Its images were analyzed by visual interpretation TAC, SUV-DC and a kinetic analysis (Patlak analysis). The latter was based on region of interest (ROIs) which were drawn with the lungdisease shape. Each optimized patterns were compared with itself. In TAC patterns, it hard to observe cancer type with inflammation disease in early pool blood area but over the time cancer type slope more remarkably increased than inflammation disease. SUV-DC was similar to TAC pattern. In the result of Patlak analysis, In time activity curve of aorta, even though inflammation disease showed higher blood activity than cancer, at first as time went by, blood activity of inflammation disease became the lowest. However, in time activity curve of tissue, cancer had the highest uptake and inflammation disease was in the middle. Through the examination, TAC and SUV-DC could approached the results that lung

Full Text Available Vitamin D deficiency is linked to accelerated decline in lung function, increased inflammation, and reduced immunity in chronic lungdiseases. Epidemiological studies have suggested that vitamin D insufficiency is associated with low lung function in susceptible subjects who are exposed to higher levels of environmental agents (airborne particulates. Recent studies have highlighted the role of vitamin D and vitamin D receptor (VDR in regulation of several genes that are involved in inflammation, immunity, cellular proliferation, differentiation and apoptosis. Vitamin D has also been implicated in reversal of steroid resistance and airway remodeling, which are the hallmarks of chronic obstructive pulmonary disease (COPD and severe asthma. VDR protein level is decreased in lungs of patients with COPD and VDR deficient mice. These mice develop an abnormal lung phenotype with characteristics of COPD, such as airspace enlargement and decline in lung function associated with increased lung inflammatory cellular influx, and immune-lymphoid aggregates formation. Dietary vitamin D may regulate epigenetic events, in particular on genes which are responsible for COPD susceptibility. Active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 plays an essential role in cellular metabolism and differentiation via its nuclear receptor (VDR that cooperates with several other chromatin modification enzymes (HATs, and HDACs, thus result in mediating complex epigenetic events in vitamin D signaling and metabolism. This review provides an update on the current knowledge and understanding on vitamin D, and susceptibility of chronic lungdiseases in relation to the possible role of epigenetics in its molecular action. Understanding the molecular epigenetic mechanisms of vitamin D/VDR would provide rationale for dietary vitamin D-mediated intervention in prevention and management of chronic lungdiseases linked with vitamin D deficiency.

manually segmented. After normalization for lung size, changes in lung dimensions between inspiration and expiration were used for analysis; normalization was based on the cranial-caudal length ratio (representing vertical diaphragmatic displacement), and the anterior-posterior and left-right length ratios...... (representing chest-wall movements due to thoracic muscles). Results: We observed striking dysfunction of the diaphragm in Pompe patients; in some patients the diaphragm did not show any displacement. Patients had smaller cranial-caudal length ratios than volunteers (p

Objective To investigate the level of interleukin (IL) -9 in patients with connective tissue disease (CTD) and connective tissue disease with interstitial lungdisease (CTD-ILD) ,and explore the role of IL-9 in the pathogenesis of CTD and CTD-ILD.Methods Sixty-one hospitalized untreated CTD patients were recruited and 20healthy volunteers were enrolled as healthy controls.Patients in the CTD group included 19 systemic sclerosis (SSc) patients,15 rheumatoid arthritis (RA) patients,

Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lungdisease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lungdisease. Here, we provide a concise overview and update on host-pathogen interactions in CF lungdisease. PMID:26905568

Occupational diseases of respiratory tract are listed among 12 independent nosological unites at the registry of the Slovak republic, (tuberculosis and lung cancer due to chemical carcinogens were excluded and listed elsewhere). In the past 10 years approximately 100 new cases of newly detected professional respiratory diseases have been reported. They encompass about 10% of all occupational diseases, ranging from 5 to 7 of all the most frequent occupational diseases. Pneumoconiosis, allergic and lung cancer represent currently the most frequent and paralinguistic the most serious occupational diseases. Pneumoconiosis represents an acute and chronic lungdisease caused by inhalation and retention of inorganic dust. Silicosis is the most frequently reported pneumoconiosis in our region. It is a progressive aseptic inflammation of lung interstitium, due to long term inhalation and deposition of mineral dust containing free crystalic SiO2 followed by a fibrotic remodeling. The x-ray manifestation without an obvious symptomatology at the beginning of disease is quite common for pneumoconiosis in general. Therefore international standards have been generated in order to describe, quantify these x-ray changes, s.c. ILO Classification. The standard chest radiograph is currently, at justified cases, accompanied by modern diagnostic CT related methods. Besides obligatory function diagnostics, microscopic and cultivation examinations, new modern facultative tests are also available for the purpose of differential diagnostics, allowing to identify diseases with a similar clinical pattern. (authors)

Chronic beryllium disease (CBD) is a debilitating lung disorder in which exposure to the lightweight metal beryllium (Be) causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of noncaseating pulmonary granulomas. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the severe host inflammatory response. Studies in the past several years have begun to highlight cell-cell adhesion interactions in the development of Be hypersensitivity and CBD. In particular, the high binding affinity between intercellular adhesion molecule 1 (I-CAM1) on lung epithelial cells and the {beta}{sub 2} integrin LFA-1 on migrating lymphocytes and macrophages regulates the concerted rolling of immune cells to sites of inflammation in the lung. In this review, we discuss the evidence that implicates cell adhesion processes in onset of Be disease and the potential of cell adhesion as an intervention point for development of novel therapies.

Full Text Available Most lung disorders are known to be associated to considerable modifications of surfactant composition. Numerous of these abnormalities have been exploited in the past to diagnose lungdiseases, allowing proper treatment and follow-up. Diagnosis was then based on phospholipid content, surface tension and cytological features of the epithelial lining fluid (ELF, sampled by bronchoalveolar lavage (BAL during fiberoscopic bronchoscopy. Today, it appears that the protein content of ELF displays a remarkably high complexity, not only due to the wide variety of the proteins it contains but also because of the great diversity of their cellular origins. The significance of the use of proteome analysis of BAL fluid for the search for new lungdisease marker proteins and for their simultaneous display and analysis in patients suffering from lung disorders has been examined.

Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lungdiseases. We report here a case of interstitial lungdisease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lungdisease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lungdisease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

Full Text Available Chronic obstructive pulmonary disease (COPD is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples.

The frequency and characteristics of chronic obstructive pulmonary disease (COPD) based on morphological and cytological changes in equine lungs were studied in this paper. Lungs obtained from 51 horses of different age and sex were examined grossly and tissue samples were collected for pathohistological examination. Cytological examination was done on impression smears from the tracheal bifurcation. Pathohistological preparations were stained with hematoxylin eosin (HE), toluidine blue (TB),...

Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widel...

A previously reported computer analysis has been used to provide numerical ventilation-perfusion lung scan data, for comparison with tests of airways function and results of arterial blood gas analysis in 11 patients with pulmonary embolism, 18 with asthma, and 37 with chronic obstructive lungdisease. In pulmonary embolism an index of underperfusion showed high sensitivity, and an index of ventilation-perfusion mismatching correlated well with severity (hypoxaemia). In asthma an index of und...

Background Interleukin-22 (IL-22) is involved in lungdiseases such as pneumonia, asthma and lung cancer. Lavage mirrors the local environment, and may provide insights into the presence and role of IL-22 in patients. Methods Bronchoscopic lavage (BL) samples (n = 195, including bronchoalveolar lavage and bronchial washings) were analysed for IL-22 using an enzyme-linked immunosorbent assay. Clinical characteristics and parameters from lavage and serum were correlated with lavage IL-22 concen...

Developmental deficiency in pulmonary surfactant leads to respiratory distress syndrome (RDS) in preterm infants, but all newborns may have impaired surfactant metabolism secondary to lungdisease or ventilator induced lung injury. Exogenous surfactant treatment is usually administered in conjunction with mechanical ventilation. If instead surfactant administration is followed by nasal continuous positive airway pressure (nCPAP), the treatment response appears to be more sus...

The clinical management of pulmonary embolism and deep venous thrombosis of the legs are similar and require prolonged anticoagulation therapy. The standard diagnostic approach in patients suspected of pulmonary embolism is ventilation-perfusion (V/Q) lung scan and compression ultrasonography to detect deep venous thrombosis. This retrospective study analyzed the role of V Q lung scan and compression ultrasonography in detection of thromboembolic disease. One hundred-twenty consecutive patients (65 female, 55 male) age range 18-95 (mean age 60.7) suspected for pulmonary embolism underwent concomitant V/Q lung scan and compression ultrasonography of the lower extremities. The clinical and radiographic correlation was performed. Of patients with non-diagnostic (low or intermediate probability ) lung scans, 15.4 % (14/91) received anticoagulation therapy for pulmonary embolism. This patients had either high pre-clinical suspicion for PE or underwent pulmonary arterio gram. However, there was an additional 7 % (7/91) increase in the number of patients who received anticoagulation therapy based on the results of ultrasound with confidence interval (3 %-16 %). We conclude that V/Q lung scan is a more sensitive examination for thromboembolic disease, and has a high negative predictive value. Ultrasonography of lower extremities demonstrated higher specificity and positive value. Among patients with non-diagnostic lung scan, the detection rate of thromboembolic disease is improved with addition of ultrasound

Full Text Available The clinical course of cystic fibrosis (CF varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lungdisease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C was associated with poorer lung function (p = 0.03. In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells. AGER seems to be a modifier gene of lungdisease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lungdisease.

Surfactant protein A (SP-A) is a large multimeric protein found in the airways and alveoli of the lungs. SP-A is a member of the collectin family of proteins, characterized by NH2-terminal collagen-like regions and COOH-terminal lectin domains. Although other surfactant proteins such as SP-B function to reduce surface tension in the lungs, SP-A as well as SP-D regulates the pulmonary immune response. To date, a number of studies have shown the immunoregulatory function of SP-A, mainly in the field of infectious diseases. By binding to a wide variety of pathogens, SP-A opsonizes and enhances pathogen uptake by phagocytes. In addition to the effect on pathogens, recent studies have shown that SP-A also modulates lung immune system in the area of non-infectious lungdiseases. In this review, the potential role of SP-A in the multiple aspects of pulmonary host defense will be discussed, focusing mainly on non-infectious lungdiseases such as acute and chronic pulmonary fibrosis and lung cancer. J. Med. Invest. 61: 1-6, February, 2014. PMID:24705741

Full Text Available Objectives: To develop a clinical prediction model of contribution of chronic obstructive pulmonary disease (COPD to the pathogenesis of lung cancer, by reporting the estimated prevalence and severity by GOLD criteria in a single-institution cohort of patients with newly diagnosed lung cancer. Primary objective was investigating the effects of impaired lung function with various histological cell types on crude survival, while considering the initial staging of disease extent. Materials & methods: A total of 441 patients, in this historical cohort from electronic medical records, completed spirometry prior to invasive diagnostic procedures and initial treatment of their lung cancer. All statistical analyses, including ANOVA and survival analysis, were performed using SAS version 9.1 software. Results: Estimated prevalence of COPD was 79.1% (95% confidence interval: 71.3%-82.9%. Lung function as measured by spirometry was a significant predictor of survival time in months (p<0.0001 both with and without adjusting for tumor-cell-type, age, and stage of disease. Median survival was similar (p=0.32 and longer among those patients with normal pulmonary function, those with restrictive disease patterns, and those with COPD–GOLD-1 defects. Median survival was shortest among patients with COPD–GOLD-4 impairment (p=0.001. Those patients with COPD–GOLD-2 and COPD-GOLD-3 impairment levels had intermediate survival times (p=0.003. Conclusions: This investigation suggests that strategies for early detection and slowing the progression of COPD before the development of lung cancer might increase patient survival. As demonstrated in this study, the presence and severity of COPD in lung cancer patients is an independent predictor of survival time, different from the established staging of initial extent of disease.

The lung cancer mortality has been analyzed for 2.582 miners employed from 1943 to 1961. All persons observed had three years occupation at least. Basing upon the lung cancer risk value per unit of the exposure, the assessment of the effective standard of pulmonary organ irradiation to radon progeny was elaborated and mortality excess was calcuated. Medical demography studies of morbidity and mortality were elaborated for silicosis, silicotuberculosis, lung cancer and occupational bronchitis versus the magnitude of dust and radiation exposure. Annual and cumulative exposures have been assessed for seven cohorts of miners employed and vast primary material has been accumulated for the period of 40 years (1943-1984). Intensive indice of mortality were determined for observation periods. The mortality excess was compared to cumulated radiation exposure. The lung cancer mortality excess in iron-uranium miners was 3.3 cases per 106 man-years per 1 WLM; 4.8 cases per 106 man-years per 1 WLM was assessed if first years of occupation are negected. The latent period from radiation exposure to death from lung cancer is generally ten year or more. Changes of miners labor conditions (the magnitude of dust exposure) have been reflected by the bronchi pulmonary disease structure. The input of these dieseases into the occupational lung pathology has been significantly changed with the time course. Within first 18-20 years, pneumoconiosis was the only form of occupational lung pathology in the mine, whereas occupational bronchis and lung cancers were recorded within next then years thereafter. In cohorts of longest observation period, the average age of patients was increasingly ranked versus diseases as follows: silicosis, silicotuberculosis, chronic bronchitis, and lung cancer. (Author)

Using perfusion lung scintigram with 99mTc-macroaggregated albumin at maximal expiration (E) and inspiration (I), images of the motion of the regional pulmonary areas and lung margins during ventilation ((E-I)/I) was obtained in patients with various respiratory diseases. The image of (E-I)/I consisted of positive and negative components. The former component visualized the motion of the regional pulmonary areas that corresponded with the ventilatory amplitude of the videodensigram. The sum of the positive component of (E-I)/I in both lungs correlated with the vital capacity (n = 50, r = 0.62). It was 163.5 ± 52.5 in cases with a vital capacity of more than 3.01, 94.1 ± 61.5 in primary lung cancer, 89.2 ± 44.7 in chronic obstructive lungdiseases and 69.0 ± 27.5 in diffuse interstitial pneumonia. The distribution pattern of pulmonary perfusion and the positive component of (E-I)/I matched fairly in many cases, but did not match in some cases. The negative component of (E-I)/I demonstrated the ventilatory motion of the lung margin and its decreased activity was shown in cases with hypoventilation of various causes including pleural diseases. The sum of the negative component of (E-I)/I in the both lungs correlated with the vital capacity (n = 50, r = 0.44). These results suggest that this technique is useful to estimate the regional pulmonary ventilatioin and motion of the lung margins. (author)

We have been investigating ultrahigh resolution optical coherence tomography (UHR-OCT) imaging of lung tissues using fiber super continuum sources. The high power, low-noise, Gaussian shaped supercontinuum generated with ultrashort pulses and optical fibers at several wavelengths were used as the broadband light sources for UHR-OCT. For the 800 nm wavelength region, the axial resolution was 3.0 um in air and 2.0 um in tissue. Since the lung consists of tiny alveoli which are separated by thin wall, the UHR-OCT is supposed to be effective for lung imaging. The clear images of alveoli of rat were observed with and without index matching effects by saline. In this work, we investigated the UHR-OCT imaging of lungdisease model. The lipopolysaccharide (LPS) induced acute lung injury / acute respiratory distress syndrome (ALI/ARDS) model of rat was prepared as the sample with disease and the UHR-OCT imaging of the disease part was demonstrated. The increment of signal intensity by pleural thickening was observed. The accumulation of exudative fluid in alveoli was also observed for two samples. By the comparison with normal lung images, we can obviously show the difference in the ALI/ARDS models. Since the lung consists of alveolar surrounded by capillary vessels, the effect of red-blood cells (RBC) is considered to be important. In this work, ex-vivo UHR-OCT imaging of RBC was demonstrated. Each RBC was able to be observed individually using UHR-OCT. The effect of RBC was estimated with the rat lung perfused with PBS.

Full Text Available Summary Fractional exhaled nitric oxide (FeNO is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia, in bronchiectasis, or in cases with diffuse lungdisease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lungdisease.

Diffuse lungdisease presents a variety of high-resolution CT findings reflecting its complex pathology, and provides diagnostic challenge to radiologists. Frequent modification of detailed pathological classification makes it difficult to keep up with the latest understanding. In this review, we describe a practical approach to high-resolution CT diagnosis of diffuse lungdisease, emphasizing (1) analysis of “distribution” of the abnormalities, (2) interpretation of “pattern” in relation to distribution, (3) utilization of associated imaging findings and clinical information, and (4) chronicity of the findings. This practical approach will help radiologists establish a way to interpret high-resolution CT, leading to pin-point diagnosis or narrower differential diagnoses of diffuse lungdiseases.

Although the activity of nitric oxide (NO) synthases are increased in lung tissue of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have recently been found to be decreased in cystic fibrosis. This could either be due to reduced NO formation or metabolism of NO within airway fluids. In this study, the stable NO metabolites, nitrate and nitrite, were determined in the saliva and sputum of 18 stable cystic fibrosis patients, 21 cystic fibrosis pat...

Abstract Background In neonatology the role of chest physiotherapy is still uncertain because of the controversial outcomes. Methods The aim of this study was to test the applicability in preterm infants of 'reflex rolling', from the Vojta method, in preterm neonates with lung pathology, with particular attention to the effects on blood gases and oxygen saturation, on the spontaneous breathing, on the onset of stress or pain. The study included 34 preterm newborns with mean gestational age of...

Full Text Available OBJECTIVE: The aim of this study was to assess cardiovascular involvement in patients with connective tissue disease (CTD, and determine whether interstitial lungdisease (ILD in these patients is associated with elevated cardiovascular risk. METHODS: This study evaluated a retrospective cohort of 436 CTD patients admitted to a large teaching hospital in Zhejiang province, China, along with an additional 436 participants of an annual community health screening conducted in the physical examination center who served as age- and gender-matched controls. Demographic, clinical, serologic and imaging characteristics, as well as medications used by each participant were recorded. Cardiovascular involvement was defined by uniform criteria. Correlations between clinical/serologic factors and cardiovascular involvement were determined by univariate and multivariate analyses. RESULTS: CTD patients had a significantly higher cardiovascular involvement rate than controls (64.7% vs 23.4%, with higher rates of diabetes, hypertension, and hyperlipidemia, elevated systolic and diastolic pressures, C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol, and lower albumin and high-density lipoprotein cholesterol (all p 2 years, use of moderate- to high-dose glucocorticoids, and ILD with a high alveolar inflammation score. CONCLUSION: Cardiovascular involvement is increased in CTD patients, and is associated with ILD with a higher alveolar inflammation score. Thus, early-stage echocardiography and CT scans should be used to detect potential cardiovascular complications in these patients.

To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lungdisease. We compared this technique to CT for assessing CF lungdisease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100 % (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lungdisease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lungdisease (i.e. pulmonary exacerbations). (orig.)

To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lungdisease. We compared this technique to CT for assessing CF lungdisease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100 % (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lungdisease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lungdisease (i.e. pulmonary exacerbations). (orig.)

Rationale Clinical trial design in interstitial lungdiseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial LungDisease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit internationa...

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. PMID:26491282

Full Text Available C Randall Lane, Adriano R Tonelli Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic obstructive pulmonary disease (COPD is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. Keywords: emphysema, pulmonary hypertension, mortality, prognosis, outcomes, alpha-1 antitrypsin deficiency

Alveolar recruitment is a central strategy in the ventilation of patients with acute lung injury and other lungdiseases associated with alveolar collapse and atelectasis. However, biomechanical insights into the opening and collapse of individual alveoli are still limited. A better understanding of alveolar recruitment and the interaction between alveoli in intact and injured lungs is of crucial relevance for the evaluation of the potential efficacy of ventilation strategies. We simulated human alveolar biomechanics in normal and injured lungs. We used a basic simulation model for the biomechanical behavior of virtual single alveoli to compute parameterized pressure-volume curves. Based on these curves, we analyzed the interaction and stability in a system composed of two alveoli. We introduced different values for surface tension and tissue properties to simulate different forms of lung injury. The data obtained predict that alveoli with identical properties can coexist with both different volumes and with equal volumes depending on the pressure. Alveoli in injured lungs with increased surface tension will collapse at normal breathing pressures. However, recruitment maneuvers and positive endexpiratory pressure can stabilize those alveoli, but coexisting unaffected alveoli might be overdistended. In injured alveoli with reduced compliance collapse is less likely, alveoli are expected to remain open, but with a smaller volume. Expanding them to normal size would overdistend coexisting unaffected alveoli. The present simulation model yields novel insights into the interaction between alveoli and may thus increase our understanding of the prospects of recruitment maneuvers in different forms of lung injury. PMID:20031137

High-resolution CT scans of lung parenchyma were obtained in 8 patients with pure polymyositis or dermatomyositis (PM-DM) with interstitial lung involvement. The most frequent findings were subpleural curved band-like shadows (A 2), which were demonstrated in 7 patients (88%). Open lung biopsy was performed in a case of A 2 shadow, which revealed non-specific interstitial pneumonia (chronic interstitial pneumonia, not otherwise specified). Most of the A 2 shadows gradually shrinked with steroids or immunosuppressants, and then disappeared completely or changed into subpleural curvilinear shadows (A 1). Peri-bronchovascular shadows (B) were detected in 4 patients (50%). Acute exacerbation had occurred in the two of them, but after all every B shadow reduced or disappeared with therapy. We think A 2 and B shadows are characteristic HRCT findings of interstitial lungdisease in PM-DM and their prognosis is fairly good. (author).

To reveal major principles in system of occupational lungdiseases prevention among workers engaged into extraction and usage of chrysotile asbestos, the authors specified main criteria for diagnosis of asbestos-related pulmonary diseases and signs of exposure to chrysotile dust, with identification of risk groups for occupational diseases development. The authors formulated main principles of prevention and rehabilitation for workers with asbestos-related pulmonary diseases. Special attention was paid to harmonization of all medical and technical measures aimed at prevention and liquidation of occupational asbestos-related diseases. PMID:25282798

Abstract Background: Irrreversible interstitial lungdisease (ILD) is associated with high morbidity and mortality. Palliative care needs of patients and caregivers are not routinely assessed; there is no tool to identify needs and triage support in clinical practice. Objective: The study objective was to adapt and face/content validate a palliative needs assessment tool for people with ILD. Methods: The Needs Assessment Tool: Progressive Disease-Cancer (NAT:PD-C) was adapted to reflect the p...

Full Text Available Smokers are subject to being more susceptible to the long-term effects of silica dust, whilst it remains unclear whether the joint effect of smoking and silicosis differs amongst diseases to the lungs; this study aims to address this knowledge gap. This was a historical cohort study comprised of 3202 silicotics in Hong Kong during 1981-2005 who were followed up till 31/12/2006. We estimated the standardized mortality ratio (SMR in the smoking and never smoking silicotics using the mortality rates of male general population indiscriminately by smoking status, but these SMRs were regarded as biased. We adjusted these biased SMRs using "smoking adjustment factors (SAF". We assessed the multiplicative interaction between smoking and silicosis using 'relative silicosis effect (RSE' that was the ratio of SAF-corrected SMR of smoking silicotics to the never smokers. A RSE differs significantly from one implies the presence of multiplicative interaction. A significant excess SMR was observed for respiratory diseases (lung cancer, chronic obstructive pulmonary diseases [COPD], silicosis and other diseases to the lungs (pulmonary heart disease, tuberculosis. All the 'biased-SMRs' in smokers were higher than those in never smokers, but the SAF-corrected SMRs became higher in never smokers. The RSE was 0.95 (95%CI: 0.37-3.55, 0.94 (95%CI: 0.42-2.60, and 0.81 (95%CI: 0.60-1.19 for lung cancer, COPD, and silicosis; whilst it was 1.21 (95%CI: 0.32-10.26 for tuberculosis and 1.02 (95%CI: 0.16-42.90 for pulmonary heart disease. This study firstly demonstrated the joint effect of smoking and silicosis may differ amongst diseases to the lungs, but power is limited.

In low-income countries some infections caused by nontuberculous mycobacteria are misdiagnosed as multidrug-resistant tuberculosis. In most of these settings the observation of microscopic cords is the only technique used to identify Mycobacterium tuberculosis in the laboratory. In this article we definitively demonstrate that Mycobacterium abscessus, an emerging pulmonary pathogen, also forms microscopic cords.

Rationale Neonatal respiratory distress syndrome is a restrictive lungdisease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lungdiseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function. Objectives To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function. Methods Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model. Measurements and Main Results Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes. Conclusions These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions. PMID:26863115

Full Text Available Neonatal respiratory distress syndrome is a restrictive lungdisease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF, which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lungdiseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1 were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.

Although for forty years already broncho-pulmonary pathology has been described in workers exposed to hard-metal (i.e. alloys of tungsten carbide and cobalt) and although cobalt is considered the offending agent of this hazard, these abnormalities have almost not been found after exposure to cobalt alone except in animal experiments. Recently we detected clearcut broncho-pulmonary pathology in 48 diamond polishers (i.e. nearly 1% of those exposed) attributable to the ultrafine cobalt dust from the cutting surface of polishing disks, in which it was used as a cementing matrix for microdiamonds without any tungsten carbide. Nineteen of these patients presented with a fibrosing alveolitis documented in 6 by lung biopsy and in 12 by broncho-alveolar lavage, both of which revealed characteristic multinucleated giant cells. Thirteen suffered from asthma of occupational origin, in 9 proven by cobalt-inhalation tests, and in 5 by peak flow measurements at the workplace. Sixteen had mixed bronchial and alveolar pathology or were incompletely documented. A cross-sectional study in about 200 diamond polishers showed a significant correlation between exposure to cobalt and decrease in lung function. The strikingly harmful effects of cobalt can be explained by the chronic exposure to very small particles with markedly increased solubility. The pathogenesis of the broncho-pulmonary pathology may be attributed to the cytotoxic as well as to the sensitising (i.e. allergic and/or idiosyncratic) actions of cobalt. PMID:2561412

Objective: To analyze the mean lung density (MLD) and pixel index (PI) of emphysema and chronic bronchitis using spirometric controlled quantitative CT. Methods: Forty healthy adults, 23 patients with emphysema, and 15 patients with chronic bronchitis performed lung spiral scans at 50% vital capacity (VC), and HRCT sections were acquired at carina and carina +- 5 cm at 10% VC and 90% VC. Results: At 10% VC, the MLD in patients with emphysema and chronic bronchitis decreased (the MLD were -831.8 HU and -796.8 HU, respectively) compared to healthy adults (-745.3 HU) (P < 0.01). At 90% VC, only the MLD in patients with emphysema significantly decreased (P < 0.05). PI had the same feature as MLD, but it increased. The lesions detected by quantitative CT were consistent with that demonstrated by morphology. Quantitative CT was more sensitive than PFTs. The quantitative parameters of 10% VC could detect chronic bronchitis even when CT indicated normal results. Conclusion: The combination of CT and quantitative CT can accomplish the unity of morphology and function, thus offer more diagnostic clues and make the diagnosis perfect

The authors compared the accuracy of chest radiographic and CT findings in predicting diagnoses in 118 patients with chronic diffuse infiltrative lungdisease, using three independent observers. First-choice diagnosis was correct with 57% of radiographs and 76% of CT scans (Plung biopsy was indicated with 65% of radiographs and 87% of CT scans (Plung disease

Acute pulmonary complications of sickle cell anemia are sickle cell lungdisease and bacterial pneumonias. Chronic abnormalities in lung function include a restrictive ventilatory defect and perhaps increased venous admixture to the pulmonary circulation. Coexisting sarcoidosis may complicate sickle cell anemia and interact to potentiate sickling. Sickle cell lungdisease, or acute "chest syndrome," occurs with greatest frequency in adults, is due primarily to pulmonary infarction, and may lead to cor pulmonale. On the other hand, bacterial pneumonia due to Streptococcus pneumoniae occurs with greater frequency in infancy and childhood. Mycoplasma and other organisms may also cause pneumonia with protracted illness and slow resolution. Bacteremia and meningitis may be further complications, particularly in children. Precise diagnosis of the acute febrile pulmonary episode is often difficult. In adults the illness is commonly self-limited. However, a vigorous diagnostic approach is warranted in all severely ill patients. PMID:7463492

Clinical, physiological and histological investigations on lung involvement are reported in 33 rheumatoid patients. The clinico-pathological patterns of rheumatoid lungdisease observed in 19/27 non-smoking female patients were characterized radiologically by diffuse interstitial opacities, functionally by V/Q inequality and microscopically by peribronchiolar and/or alveolar fibrosis. Emphasis is placed on the ventilation/perfusion relationship as well as histopathological studies for a more accurate diagnosis of lungdisease in RA. Patients with pulmonary nodules and pleural opacities were also observed. A possible immunological aetiology is suggested on the basis of the simultaneous finding of IgG, complement and fibrinogen in the pulmonary tissue. PMID:7209294

Chronic inflammatory lungdiseases such as cystic fibrosis and emphysema are characterized by higher-than-normal levels of pulmonary proteases. While these enzymes play important roles such as bacterial killing, their dysregulated expression or activity can adversely impact on the inflammatory process. The existence of efficient endogenous control mechanisms that can dampen or halt this overexuberant protease activity in vivo is essential for the effective resolution of inflammatory lungdisease. The function of pulmonary antiproteases is to fulfil this role. Interestingly, in addition to their antiprotease activity, protease inhibitors in the lung also often possess other intrinsic properties that contribute to microbial killing or termination of the inflammatory process. This review will outline important features of chronic inflammation that are regulated by pulmonary proteases and will describe the various mechanisms by which antiproteases attempt to counterbalance exaggerated protease-mediated inflammatory events. These proteases, antiproteases and their modifiers represent interesting targets for therapeutic intervention.

Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lungdisease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lungdisease and this case underscores the importance of the continuation of autopsies.

Smoking-induced lungdiseases were extremely rare prior to the 20th century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs-depending on the signaling pathway (nuclear factor-κB, adenosine monophosphate-activated protein kinase, c-Jun N-terminal kinase, p38, and signal transducer and activator of transcription 3) activated. Multiple proteins are upregulated and secreted in response to CS exposure, and many of these have immunomodulatory activities that contribute to disease pathogenesis. In particular, metalloproteases 9 and 12, surfactant protein D, antimicrobial peptides (LL-37 and human β defensin 2), and IL-1, IL-6, IL-8, and IL-17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking-induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS-induced diseases, including COPD, respiratory bronchiolitis-interstitial lungdisease, desquamative interstitial pneumonia, acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by secondhand and thirdhand smoke exposure and the pulmonary diseases that result. New targeted antiinflammatory therapeutic options are currently under investigation and hopefully will yield promising results for the treatment of these highly prevalent smoking-induced diseases. PMID:26135024

The objective of this study was to review the literature on bronchoalveolar lavage fluid cell profiles in healthy children and adolescents, as well as on the use of BAL as a diagnostic and follow-up tool for lungdisease patients in this age bracket. To that end, we used the Medline database, compiling studies published between 1989 and 2009 employing the following MeSH descriptors (with Boolean operators) as search terms: bronchoalveolar lavage AND cytology OR cell AND child. In healthy children, the cell profile includes alveolar macrophages (> 80%), lymphocytes (approximately 10%), neutrophils (approximately 2%) and eosinophils (< 1%). The profile varies depending on the disease under study. The number of neutrophils is greater in wheezing children, especially in non-atopic children, as well as in those with pulmonary infectious and inflammatory profiles, including cystic fibrosis and interstitial lungdisease. Eosinophil counts are elevated in children/adolescents with asthma and can reach high levels in those with allergic bronchopulmonary aspergillosis or eosinophilic syndromes. In a heterogeneous group of diseases, the number of lymphocytes can increase. Evaluation of the BAL fluid cell profile, when used in conjunction with clinical and imaging findings, has proven to be an essential tool in the investigation of various lungdiseases. Less invasive than transbronchial and open lung biopsies, BAL has great clinical value. Further studies adopting standard international protocols should be carried out. Such studies should involve various age groups and settings in order to obtain reference values for BAL fluid cell profiles, which are necessary for a more accurate interpretation of findings in children and adolescents with lungdiseases. PMID:20625676

Full Text Available Abstract Background Critical to advancing the systems-level evaluation of complex biological processes is the development of comprehensive networks and computational methods to apply to the analysis of systems biology data (transcriptomics, proteomics/phosphoproteomics, metabolomics, etc.. Ideally, these networks will be specifically designed to capture the normal, non-diseased biology of the tissue or cell types under investigation, and can be used with experimentally generated systems biology data to assess the biological impact of perturbations like xenobiotics and other cellular stresses. Lung cell proliferation is a key biological process to capture in such a network model, given the pivotal role that proliferation plays in lungdiseases including cancer, chronic obstructive pulmonary disease (COPD, and fibrosis. Unfortunately, no such network has been available prior to this work. Results To further a systems-level assessment of the biological impact of perturbations on non-diseased mammalian lung cells, we constructed a lung-focused network for cell proliferation. The network encompasses diverse biological areas that lead to the regulation of normal lung cell proliferation (Cell Cycle, Growth Factors, Cell Interaction, Intra- and Extracellular Signaling, and Epigenetics, and contains a total of 848 nodes (biological entities and 1597 edges (relationships between biological entities. The network was verified using four published gene expression profiling data sets associated with measured cell proliferation endpoints in lung and lung-related cell types. Predicted changes in the activity of core machinery involved in cell cycle regulation (RB1, CDKN1A, and MYC/MYCN are statistically supported across multiple data sets, underscoring the general applicability of this approach for a network-wide biological impact assessment using systems biology data. Conclusions To the best of our knowledge, this lung-focused Cell Proliferation Network

Introduction Interstitial lungdisease can be idiopathic or occur in the setting of connective tissue diseases. In the latter case it requires a different treatment approach with a better prognosis. Interstitial lungdisease can precede the onset of typical connective tissue disease features by many years, and therefore meticulous multidisciplinary follow-up is crucial. This case highlights the diagnostic challenge and the need for intensified attention for subtle clinical features when faced...

Gallium 67 has been used as a modality to diagnose and follow the clinical course of diseases such as tumors, infections, inflammatory disorders, and interstitial lungdisease. It has been appreciated, however, that mild to moderate changes in scan activity, when these disorders are followed over time, are less than optimal. SPECT (single-photon emission computed tomography) scanning is a new technique designed to obviate this problem. SPECT scanning utilizes computer acquisition to provide three-dimensional scanning and the additional benefit of colorization to aid in discerning differences of uptake. SPECT scanning was performed on 22 patients with interstitial lungdisease of various etiologies. Additionally, 7 patients had follow-up SPECT scanning to determine their response to treatment. Two patients are presented as examples

To assess whether long-term inhalation with hypertonic saline is able to halt the progression of mild CF lungdisease, we analysed longitudinal data of lung clearance index (LCI) and spirometry. A total of 34 patients with mild lungdisease (FEV1 ≥ 70% of predicted) had at least one LCI result before and ≥2 LCI measurements after start of hypertonic saline (HS) therapy. After a mean follow-up of 39.7 (SD 7.4) months after starting HS, LCI improved significantly from 7.89 (SD 1.35) at baseline to 6.96 (SD 1.03), and 19/34 patients had a normal LCI value at the last measurement. No decrease in mean FEV1 was observed. Thus, ventilation inhomogeneity can improve in patients with mild lungdisease. PMID:26190829

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease. PMID:26182407

In patients with chronic inflammatory lungdisease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role.

Full Text Available Mixed Connective Tissue Disorder (MCTD is an overlap syndrome with features predominantly of Systemic Lupus Erythematosus (SLE, polymyositis-dermatomyositis and scleroderma. Pleuropulmonary complications are common among this group of patients. Interstitial lungdiseases are most common pulmonary complications.

We studied 306 patients with chest pain (262 with coronary artery disease and 44 with no coronary artery disease) to determine which of 23 clinical, exercise, thallium, and angiographic variables best discriminate between patients with increased lung/heart ratios of thallium versus those with normal ratios. Normal lung/heart ratio values were defined using an additional 45 subjects with less than 1% probability of coronary artery disease. The number of diseased vessels was the best discriminator between patients with increased ratios versus those with normal ratios. Double product at peak exercise, number of segments with abnormal wall motion, patient gender, and duration of exercise were also significant discriminators. Using discriminant function analysis these variables could correctly identify 81% of cases with increased lung/heart ratios and 72% of cases with normal ratios. These results indicate that an increased lung/heart ratio of thallium reflects exercise-induced left ventricular dysfunction and affords a better understanding of why this thallium parameter is a powerful prognostic indicator in patients with chest pain

The objective of this study was to determine whether insulin administration would prevent the well-documented catabolic effect of dexamethasone given to preterm infants with chronic lungdisease. We studied leucine metabolism in 11 very-low-birth-weight infants before dexamethasone treatment and on

Magnetic resonance imaging (MRI) gains increasing importance in the assessment of cystic fibrosis (CF) lungdisease. The aim of this study was to develop a morpho-functional MR-scoring-system and to evaluate its intra- and inter-observer reproducibility and clinical practicability to monitor CF lungdisease over a broad severity range from infancy to adulthood. 35 CF patients with broad age range (mean 15.3 years; range 0.5–42) were examined by morphological and functional MRI. Lobe based analysis was performed for parameters bronchiectasis/bronchial-wall-thickening, mucus plugging, abscesses/sacculations, consolidations, special findings and perfusion defects. The maximum global score was 72. Two experienced radiologists scored the images at two time points (interval 10 weeks). Upper and lower limits of agreement, concordance correlation coefficients (CCC), total deviation index and coverage probability were calculated for global, morphology, function, component and lobar scores. Global scores ranged from 6 to 47. Intra- and inter-reader agreement for global scores were good (CCC: 0.98 (R1), 0.94 (R2), 0.97 (R1/R2)) and were comparable between high and low scores. Our results indicate that the proposed morpho-functional MR-scoring-system is reproducible and applicable for semi-quantitative evaluation of a large spectrum of CF lungdisease severity. This scoring-system can be applied for the routine assessment of CF lungdisease and maybe as endpoint for clinical trials.

Full Text Available Background and objective To determine the value of mediastinoscopy in the mediastinal staging of lung cancer with clinical N2 disease. Methods We retrospectively reviewed 87 patients received mediastinoscopy for known or suspected lung cancer, including 83 cervical mediastinoscopies and 4 parasternal mediastinoscopies. All patients were staged clinical N2 for enlarged ipsilateral mediastinal and/or subcarinal lymph nodes (short axis > 1.0 cmon computed tomography scan. Results Of the 87 patients, 61 cases proved N2 disease on mediastinoscopy. The other 26 mediastinoscopy-negative patients underwent thoracotomy for lung resection and mediastinal lymph node dissection in the same operative session. Final pathologic N staging were consistent for mediastinoscopic sampling and surgical dissection in 24 patients. N2 disease was found in 2 patients (false-negative of mediastinoscopy. The sensitivity, specificity, and accuracy of mediastinoscopy were 96.8%, 100%, and 97.7%, respectively. There was no mortality and only 1 complication(1.1% for all 87 mediastinoscopic procedures. Conclusion Mediastinoscopy is a highly effective and safe procedure for the mediastinal staging of lung cancer with clinical N2 disease.

Full Text Available Infiltrative lungdisease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

Fibrosis Trials Register: 29 August 2013. SELECTION CRITERIA: Randomized controlled studies and quasi-randomized controlled studies of people with cystic fibrosis comparing antioxidants as listed above (individually or in combination) in more than a single administration to placebo or standard care. DATA...... COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed the risk of bias in the included studies. We contacted trial investigators to obtain missing information. Primary outcomes are lung function and quality of life; secondary outcomes are oxidative stress......, inflammation, nutritional status, days on antibiotics and adverse events during supplementation. If meta-analysed, studies were subgrouped according to method of administration and the duration of supplementation. MAIN RESULTS: One quasi-randomized and nine randomized controlled studies were included, with a...

ABSTRACT In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lungdiseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including les...

Objective Chronic inflammation and fibrosis are characteristic of interstitial lungdiseases (ILD) and are accompanied by neovascularisation. The aim of this study was to examine the relationship between the angiogenic activity of sera from ILD patients and pulmonary function tests. Material and methods Serum samples were obtained from 225 ILD patients: 83 with sarcoidosis, 31 with idiopathic pulmonary fibrosis, 29 with extrinsic allergic alveolitis, 16 with collagen vascular diseases, 13 wit...

Purpose Some patients with interstitial lungdisease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. Materials and Methods A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We a...

Background The opinions held by the general population on obstructive lungdisease and inhaler devices could influence asthma and chronic obstructive pulmonary disorder (COPD) management and treatment adherence. The aim of the present public pragmatic survey was to evaluate the opinions, beliefs and perceptions of Italian people with respect to respiratory diseases as well as their perspectives on the use of inhaler devices. Methods This survey was conducted on a group of 2,008 individuals fo...

Background Adult patients with cystic fibrosis (CF) frequently have reduced exercise tolerance, which is multifactorial but mainly due to bronchial obstruction. The aim of this retrospective analysis was to determine the mechanisms responsible for exercise intolerance in patients with mild-to-moderate or severe disease. Methods Cardiopulmonary exercise testing with blood gas analysis at peak exercise was performed in 102 patients aged 28 ± 11 years: 48 patients had severe lungdisease (FEV1 ...

Significance: Bronchopulmonary dysplasia (BPD), also known as chronic lungdisease of infancy, is a major complication of preterm birth that, despite improvements in neonatal respiratory support and perinatal care, remains an important cause of morbidity and mortality, often with severe adverse neurodevelopmental sequelae. Even with major advances in our understanding of the pathogenesis of this disease, BPD remains essentially without adequate treatment. Recent Advances: Cell-based therapies...

After a mathematical extension of the existing model for the theoretical description of the aerosol bolus dispersion, the behavior of particle pulses in diseasedlung structures was simulated. The geometry used for healthy lungs was modified in two aspects: First, a modelling of possible airway obstructions, which usually occur in patients with chronic bronchitis, chronic asthma or cystic fibrosis, was carried out and, second, a theoretical approximation of the emphysema, being observed in lungs of smokers, but also as an accompanying phenomenon in obstructive diseases, was established. According to the modified model, in lungs with airway obstructions the exhaled bolus exhibited a decreased dispersion with respect to healthy subjects, whereas in emphysematous lungs the respective half-width of the peak was increased. Standard deviation and skewness of the bolus were similarly influenced by the modified lung architecture. A combination of airway obstruction and emphysema caused an extensive compensation of individual dispersion effects, complicating a secure distinction from the healthy lung. According to the model, a special diagnostic value may be assigned to the bolus deposition, showing significant deviations from the normal case for all simulated diseases. (orig.)

The risk of developing radiation-induced lung cancer is currently estimated using models based on epidemiological data from populations exposed either to relatively uniform, low-LET radiation, or from uranium miners exposed to radon and its progeny. Because inhaled alpha-emitting radionuclides (e.g., Pu, Am) produce nonuniform, chronic irradiation of the parenchymal region of the lung, a better scientific basis is needed for assessing the risk of developing radiation-induced disease from these radionuclides. Scientists at FIB-1 and LRRI are using a unique resource at the FIB-1, i.e., a set of about 600 lung specimens fixed in 10% formalin, and obtained from a population of workers at the Mayak Production Association, many of whom inhaled significant quantities of Pu and other alpha-emitting radionuclides during their careers. The objectives of this research are to measure the microscopic distribution of Pu by quantitative autoradiography, to determine the spatial distribution of Pu in human lung tissue with respect to specific lung structures and to determine the effect of chronic tobacco-smoke exposure on the distribution of local Pu radiation dose. The approach to analyzing these lung samples is to utilize contemporary stereological sampling and analysis techniques together with quantitative alpha-particle autoradiography. Our initial results have validated the usefulness of these lung specimens for determining Pu particle distribution with respect to anatomic location, as well as identifying normal and diseased compartments in the lung. In brief, particles were most often found associated with parenchymal and nonparenchymal scars, with other particles in organized lymphoid tissue or the interstitium of the pulmonary parenchyma (respiratory bronchioles and alveolar region). Based on comparison of one lung from a smoker and one from a nonsmoker, there was an increased fraction of Pu particles associated with tissue scars in the smoker vs the nonsmoker, and this

Advanced restrictive lungdiseases remain a challenge for both the clinician and patient alike. Because there are few available treatment options that prolong survival for patients with diseases such as idiopathic pulmonary fibrosis, improvement in quality of life and palliation of significant symptoms become realistic treatment goals. Several validated instruments that assess quality of life and health-related quality of life have demonstrated the dramatic impact that lungdisease has on patients. Quality-of-life assessments of patients with interstitial lungdisease have commonly cited respiratory complaints as problematic, but other distressing symptoms often not addressed include fear, social isolation, anxiety, and depression. Not only do respiratory symptoms limit this patient population, but the awareness of decreased independence and ability for social participation also has an impact on the quality of life. Some patients describe a deepened spiritual well-being during their disease process; however, many patients' mental health suffers with experiences of fear, worry, anxiety, and panic. Many patients express desire for more attention to end-of-life issues from their physicians. Fears of worsening symptoms and suffocation exist with an expressed desire by most to die peacefully with symptom control. Interventions to improve quality of life are largely directed at symptom control. Pharmacologic and nonpharmacologic interventions have been helpful in relieving dyspnea. Studies have demonstrated that the use of supplemental oxygen in the face of advancing hypoxemia can have both positive and negative effects on quality of life. Patients using nasal prongs describe feelings of self-consciousness, embarrassment, and social withdrawal. Pulmonary rehabilitation is recommended, with some studies noting increased quality-of-life scores and decreased sensations of dyspnea. Sleep deprivation and poor sleep quality also have a negative impact on quality of life

The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case-control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown. We...... genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded. In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever...

The proteinase-antiproteinase hypothesis still receives support from clinical and experimental observations in a range of inflammatory lungdiseases. The function of these molecules appears to be broader than originally believed and further research is likely to lead to an improved understanding of their role in the regulation of both the beneficial and detrimental effects in inflammatory response and the maintenance of the homeostasis in the normal lung. Thus the potential for the development as therapeutic tools is likely to become more attractive as improved drug development and delivery mechanisms appear. PMID:11527014

Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

Pulmonary surfactant is a mixture of lipids and hydrophobic surfactant proteins B (SP-B) and SP-C and hydrophilic proteins SP-A and SP-D. Pulmonary surfactant reduces the surface tension at the air-water interface of the lung alveoli by forming a surface active film. In this way, it prevents alveoli from collapsing and facilitates the process of breathing. SP-C cooperates with SP-B to enhance the surface active properties of surfactant phospholipids. Reports on the association of lungdisease...

Novel hydrolytically stable gelatin nanofibers modified with sodium or calcium salt of oxycellulose were prepared by electrospinning method. The unique inhibitory effect of these nanofibers against Escherichia coli bacteria was examined by luminometric method. Biocompatibility of these gelatin/oxycellulose nanofibers with eukaryotic cells was tested using human lung adenocarcinoma cell line NCI-H441. Cells firmly adhered to nanofiber surface, as determined by scanning electron microscopy, and no signs of cell dying were detected by fluorescent live/dead assay. We propose that the newly developed gelatin/oxycellulose nanofibers could be used as promising scaffold for lungdisease modeling and anti-cancer drug testing. PMID:27287147

A case of debilitating cavitating lungdisease associated with rheumatoid arthritis and bronchocentric granulomatosis, which failed to respond to conventional medical or surgical treatment, is described. The patient was treated over 10 years with steroids, antimicrobial agents, disease-modifying antirheumatoid drugs and surgery. Lung function continued to decline and the patient presented for admission with recurrent pneumonia. Abatacept was initiated to modify the underlying immunopathology. Following 12 months of treatment with abatacept the patient has demonstrable improvement in lung function and lung anatomy, and has not presented to hospital with pneumonia. She has tolerated the treatment without complication. The use of abatacept has stabilised the lungdisease in this case in the medium term and prevented readmission to hospital. These results suggest a larger role for abatacept in those with such disease in the future and may warrant further investigation.

Lung antimicrobial proteins and peptides (AMPs) are major sentinels of innate immunity by preventing microbial colonization and infection. Nevertheless bactericidal activity of AMPs against Gram-positive and Gram-negative bacteria is compromised in patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and asthma. Evidence is accumulating that expression of harmful human serine proteases, matrix metalloproteases and cysteine cathepsins is markedely increased in these chronic lungdiseases. The local imbalance between proteases and protease inhibitors compromises lung tissue integrity and function, by not only degrading extracellular matrix components, but also non-matrix proteins. Despite the fact that AMPs are somewhat resistant to proteolytic degradation, some human proteases cleave them efficiently and impair their antimicrobial potency. By contrast, certain AMPs may be effective as antiproteases. Host proteases participate in concert with bacterial proteases in the degradation of key innate immunity peptides/proteins and thus may play immunomodulatory activities during chronic lungdiseases. In this context, the present review highlights the current knowledge and recent discoveries on the ability of host enzymes to interact with AMPs, providing a better understanding of the role of human proteases in innate host defense. PMID:26341472

Full Text Available Introduction: Pulmonary involvement is the most common cause of mortality and disability in patients with systemic sclerosis and it significantly affects the quality of life in these patients. Therefore, early diagnosis and treatment of pulmonary involvement seems necessary in patients with SSc. In this study, we aimed to assess the health-related quality of life (HRQoL in patients with Scleroderma-Interstitial LungDisease (SSc-ILD and its relationship with pulmonary function parameters. Materials and Methods: Considering the inclusion and exclusion criteria, 25 patients with SSc-ILD were enrolled in this cross-sectional study from April 2012 to June 2013. Full tests of lung function, including body plethysmography and diffusing capacity of the lungs for carbon monoxide (DLCO, 6-minute walk distance (6MWD, and pulse oximetry were performed. The HRQoL was assessed using St. George’s and CAT questionnaires; also, dyspnea was evaluated for all the patients, using modified medical research council (MMRC scale. Afterwards, the relationship between the total scores of HRQoL questionnaires and the severity of lungdisease was analyzed, based on the recorded variables. Results: The mean age of the patients was 40.36±9.50 years and the mean duration of the disease was 7.16±4.50 years. A statistically significant inverse correlation was observed between 6MWD (r=-0.50, P=0.01, DLCO (r=-0.67, P

Bronchial anthracofibrosis (BAF), an emerging pulmonary disease due to long-standing exposure to biomass fuel smoke, is predominantly seen in females from developing nations. BAF is known to be associated with tuberculosis, pneumonia, chronic obstructive pulmonary disease and lung cancer, but the association of BAF with interstitial lungdisease (ILD) is rare and yet to be highlighted. A 72-year-old woman with a 30-year history of exposure to biomass fuel smoke presented with dry cough and exertional dyspnoea. Imaging demonstrated interlobular, intralobular and peribronchovascular interstitial thickening and honeycombing adjoining the subpleural regions, suggestive of the usual interstitial pneumonia pattern. A restrictive pattern with diffusion defect was noted. Fibrebronchoscopy revealed a bluish-black anthracotic pigmentation with a narrowed and distorted left upper lobe, and apical segment of left lower lobe bronchus, confirming BAF. A diagnosis of BAF with ILD was made. To the best of our knowledge, this is the first detailed description of this association. PMID:26759407

Full Text Available No single animal model can reproduce all of the human features of both acute and chronic lungdiseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lungdisease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

Cystic fibrosis (CF) is a multiorgan disease caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. Obstructive lungdisease is the predominant cause of morbidity and mortality; thus, most efforts to improve outcomes are directed toward slowing or halting lung-disease progression. Current therapies, such as mucolytics, airway clearance techniques, bronchodilators, and antibiotics, aim to suppress airway inflammation and the processes that stimulate it, namely, retention and infection of mucus plaques at the airway surface. New approaches to therapy that aim to ameliorate specific CFTR mutations or mutational classes by restoring normal expression or function are being investigated. Because of its sensitivity in detecting changes associated with early airway obstruction and regional lungdisease, high-resolution CT (HRCT) complements pulmonary function testing in defining disease natural history and measuring response to both conventional and experimental therapies. In this review, perspectives on the genetics and microbiology of CF provide a context for understanding the increasing importance of HRCT and other imaging techniques in assessing CF therapies. (orig.)

Cystic fibrosis (CF) is a multiorgan disease caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. Obstructive lungdisease is the predominant cause of morbidity and mortality; thus, most efforts to improve outcomes are directed toward slowing or halting lung-disease progression. Current therapies, such as mucolytics, airway clearance techniques, bronchodilators, and antibiotics, aim to suppress airway inflammation and the processes that stimulate it, namely, retention and infection of mucus plaques at the airway surface. New approaches to therapy that aim to ameliorate specific CFTR mutations or mutational classes by restoring normal expression or function are being investigated. Because of its sensitivity in detecting changes associated with early airway obstruction and regional lungdisease, high-resolution CT (HRCT) complements pulmonary function testing in defining disease natural history and measuring response to both conventional and experimental therapies. In this review, perspectives on the genetics and microbiology of CF provide a context for understanding the increasing importance of HRCT and other imaging techniques in assessing CF therapies. (orig.)

Rationale : The relationship between erectile dysfunction (ED) and chronic diseases, most notably diabetes and atherosclerosis, is well established. Previous studies have shown a relationship between COPD and ED. The pathogenesis is not clearly established, but studies have shown a correlation be...

Background Exercise training is of benefit for patients with restrictive lungdisease. However, it tends to be intolerable for those with severe disease. We examined whether providing ventilatory assistance by using negative pressure ventilators (NPV) during exercise training is feasible for such patients and the effects of training. Methods 36 patients with restrictive lungdisease were prospectively enrolled for a 12-week multidisciplinary rehabilitation program. During this program, half o...

Case Report: A 60-year-old female patient underwent craniotomy for a cerebral lesion in the frontoparietal lobe. Histologically, it turned out to be a metastasis from an adenocarcinoma. The primary tumor was found in the upper lobe of the left lung. The patient had whole brain radiation therapy only, the lung tumor was not treated. 4 years later, she presented with enlarged cervical lymph nodes. A biopsy showed dilated sinuses filled with histiocytes, but no tumor cells. The diagnosis of sinus histiocytosis with massive lymphadenopathy was made (Rosai-Dorfman's disease). Without any treatment, the swelling resolved completely a few weeks later. Similar episodes were observed several times in the following years. The patient died more than 7 years after the diagnosis of a metastasizing lung cancer due to pneumonia. Conclusion: In a patient with a pulmonary neoplasm and suspected supraclavicular lymph node spread, Rosai-Dorfman's syndrome should be considered as a rare differential diagnosis. (orig.)

The mortality of uranium miners from both lung cancer and other respiratory diseases is strongly dependent on exposure to radon daughters, cigarette smoking, and height. Lung cancer among 15 different mining groups was analyzed to determine what factors influence incidence and the induction-latent period. At low exposures or at low exposure rates, alpha radiation is more efficient in inducing lung cancer, producing an upward convex exposure-response curve. The induction-latent period is shortened by an increased age at the start of mining, by cigarette smoking, and by high exposure rates. For follow-up periods of 20 to 25 years, the incidence increases with age at the start of mining, with the magnitude of exposure, and with the amount of cigarette smoking. Instead of extrapolating downward from high exposures to estimate risk at low levels, it might be more appropriate to use cancer rates associated with background radiation as the lowest point on the exposure-response curve

The aim of this study was to investigate the distribution of specific phenotypes in patients with lungdiseases as well as their eventual association with the risk of developing lungdiseases. For this purpose 2777 patients with lungdiseases and 2778 healthy individuals from all over Kosova were examined for the appearance of the following selected phenotypes: ear lobe free (ELF)/ear lobe attached, normal chin (NC)/cleft chin, tongue roller (TR)/non roller, hand clasping right thumb over (HC)/hand clasping left thumb over, righthanded (RH)/lefthanded. In addition, the blood group from ABO system and the presence or absence of the Rhesus factor asphenotypical markers were observed. The results obtained show significant differences between control and lungdisease patients for NC (p ≤ 0.05) and TR (p ≤ 0.005) as well as for blood groups AB (p ≤ 0.05) and O (p ≤ 0.005). These results point to eventually increased levels of genetic load as a result of the increased homozygosity in some gene loci causing an increased frequency of some recessive phenotypes in patients with lungdiseases. Together with the specific associations observed, these preliminary findings could serve as a basis for further in depth investigations with respect to the types of lungdiseases, occupational exposure and dietary habits, and thus is expected to contribute to an understanding of predispositions and susceptibility to lungdiseases. PMID:26987159

Full Text Available Objective: To evaluate the role of bronchoalveolar lavage (BAL in patients with interstitial lungdisease associated to antisynthetase syndrome. Methods: We describe 5 patients, anti-Jo1 positive, with interstitial lungdisease (lung fibrosis and/or diffusion capacity of CO <80%. Patients were monitored with lung function tests every 6 months, with high-resolution computed tomography (HRCT every 12 months, and with bronchoalveolar lavage (BAL at baseline and in the subsequent follow-up. Patients were treated as follows: a azathioprine with colchicine, or cyclosporine alone b cyclophosphamide when high neutrophil or eosinophil count on BAL was observed. Only low-dose steroids were used for mild muscular or articular involvement. Results: Pulmonary involvement remained stable in all patients at months +24. Lung function remained unchanged compared to the baseline evaluation; HRCT was stable in patients with fibrosis and no progression into fibrosis was observed in patients with ground glass areas at baseline. Bacterial pneumonia occurred in one patient treated with cyclophosphamide and resolved after antibiotic therapy. Conclusions: Clinical manifestations, instrumental tests and BAL may be of value to choice the best immunosuppressive therapy in the single case. An early less aggressive approach (azathioprine with colchicine, or cyclosporine alone may be useful. BAL could be performed when a progression of the lung involvement is demonstrated in the subsequent follow-up. Cyclophosphamide may be a valid alternative treatment in the presence of a neutrophilic or eosinophilic alveolitis. Efficacy and safety of the aforementioned immunosuppressive approach were observed in our series, avoiding prolonged high-dose steroid administration.

Full Text Available BACKGROUND: Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID of the brain is protective against the development of brain metastases in lung cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the brain as part of their standard initial staging evaluation was reviewed. Information collected included demographics, comorbidities, details of the lung cancer, and the presence of SVID of the brain. A portion of the cohort had the degree of SVID graded. The primary outcome measure was the portion of study subjects with and without SVID of the brain who had evidence of brain metastases at the time of initial staging of their lung cancer.109 patients (20.8% had evidence of brain metastases at presentation and 345 (66.0% had evidence of SVID. 13.9% of those with SVID and 34.3% of those without SVID presented with brain metastases (p<0.0001. In a model including age, diabetes mellitus, hypertension, hyperlipidemia, and tobacco use, SVID of the brain was found to be the only protective factor against the development of brain metastases, with an OR of 0.31 (0.20, 0.48; p<0.001. The grade of SVID was higher in those without brain metastases. CONCLUSIONS/SIGNIFICANCE: These findings suggest that vascular changes in the brain are protective against the development of brain metastases in lung cancer patients.

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosc...

Honeycombing in general is a sign of severe end-stage fibrosis. Here we present two cases, where the combination of emphysema, acute inflammation and pulmonary embolism gave an appearance of honeycombing seen in pulmonary fibrosis. HRCT interpretation in the evaluation of acutely ill patients with pulmonary infection is a challenge. Our case reports emphasize the importance of a multidisciplinary approach, when it comes to patients with suspected complicated pulmonary diseases. At the same ti...

Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of dise...

BACKGROUND: Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA). Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD. In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer. METHODS: Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 w...